The DOI matches its Crossref record; 50 of the 52 references it cites were found in a registry or an index; none of the 36 sources its claims cite is checked for support yet.
Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop
Open accessAbstract
Neurons propagate information through circuits by integrating thousands of synaptic inputs to generate an action potential output. Inputs from different origins are often targeted to distinct regions of a neuron’s dendritic tree, with synapses on more distal dendrites normally having a weaker influence on cellular output compared to synapses on more proximal dendrites. Here we report that hippocampal CA2 pyramidal neurons, whose function has remained obscure for 75 years, have a reversed synaptic strength rule. Thus, CA2 neurons are strongly excited by their distal dendritic inputs from entorhinal cortex but only weakly activated by their more proximal dendritic inputs from hippocampal CA3 neurons. CA2 neurons in turn make strong excitatory synaptic contacts with CA1 neurons. In this manner CA2 neurons form the nexus of a highly plastic disynaptic circuit linking the cortical input to the hippocampus to its CA1 neuronal ouput. This circuit is likely to mediate key aspects of hippocampal-dependent spatial memory.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This paper shows that hippocampal CA2 pyramidal neurons obey a reversed synaptic-strength rule: distal entorhinal cortical inputs strongly excite them, while proximal CA3 inputs are weak and inhibition-dominated. CA2 neurons in turn form unusually strong excitatory connections onto CA1 neurons, defining a plastic disynaptic cortico-hippocampal loop.
Key findings
- Distal entorhinal inputs drive CA2 far more strongly than CA1: LIII stimulation (20 V) evoked EPSPs of 9.4 ± 1.2 mV in CA2 versus 1.9 ± 0.4 mV in CA1 (n = 10 vs 8, p < 0.001); LII stimulation (20 V) evoked 7.4 ± 0.9 mV in CA2 versus 2.8 ± 0.8 mV in CA3 (n = 8 vs 6, p < 0.003).
- Proximal CA3/Schaffer collateral inputs are weaker onto CA2 and dominated by feed-forward inhibition: SC EPSPs were 10.8 ± 2.2 mV in CA2 versus 17.5 ± 2.6 mV in CA1 (n = 7 vs 8, p = 0.008), with similar IPSPs, giving EPSP/IPSP < 1 in CA2 versus ~2 in CA1. With inhibition intact, LIII stimulation fired CA2 in 20% of cells (3/15) but not CA1; with inhibition blocked, LIII fired 80% of CA2 neurons (12/15) but only 1/12 CA1 neurons.
- Cortical synapses onto CA2 express robust LTP: LIII–CA2 fEPSPs potentiated to 162.5 ± 9.1% (n = 9) versus 127.1 ± 5.4% at LIII–CA1 (n = 7, p = 0.01); LII–CA2 LTP was 194.3 ± 9.8% (n = 6) versus 135.1 ± 9.3% at LII–CA3 (n = 6, p = 0.0008). SC–CA2 LTP was weak/transient (108.9 ± 4.2%, n = 9) versus CA1 (153.5 ± 13.0%, n = 9, p = 0.006).
- CA2–CA1 unitary connections are strong: connectivity was ~5% (5 out of ~100 pairs tested), success probability 0.4–0.6, and potency ~−8 pA versus ~−4 pA reported for CA3–CA1; EPSC successes showed multiple equally spaced peaks around −5 pA. LIII stimulation could drive CA2 firing and then a late polysynaptic CA1 response/action potential; cutting between CA2 and CA1 abolished this (n = 8), while cutting between CA3 and CA2 preserved it in 4/6 experiments.
Methods
- Acute transverse hippocampal slices from 4–6 week old C57BL6 male mice; whole-cell current-clamp recordings from CA1, CA2, and CA3 pyramidal neurons, extracellular field recordings, and paired CA2–CA1 recordings.
- Synaptic inputs were activated by focal stimulation in stratum lacunosum moleculare (LIII EC), dentate molecular layer (LII EC), and stratum radiatum (Schaffer collaterals); inhibitory transmission was blocked with picrotoxin and CGP 55845A, and polysynaptic DG→CA3→CA2 responses were blocked with DCG-IV.
- CA2 identity was confirmed by electrophysiological criteria, morphology, fluorescent dye filling, and post hoc α-actinin 2 immunolabeling. LTP was induced by tetanic stimulation (100 pulses at 100 Hz, repeated twice at 20 s intervals) and measured 40–50 min after induction versus baseline; comparisons used Student’s t-test, reported as mean ± SEM.
Limitations
- Stated: paired CA2–CA1 connectivity was very low (~5%, 5 out of ~100 pairs tested), limiting detailed characterization; only three of five connected pairs were studied with dual whole-cell recordings and two with extracellular stimulation of a single CA2 neuron.
- Stated: additional studies are needed to elucidate the dendritic mechanisms underlying differential EPSP propagation in CA2 versus CA1, and future chemical or genetic lesions of CA2 are needed to define its role in the intact hippocampus.
- Evident: all experiments are in acute hippocampal slices from young adult male mice, so circuit function, memory roles, and in vivo firing inferences are not directly tested here; the authors address some slice-artifact concerns with field recordings and comparisons to prior in vivo work, but the study remains in vitro.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 36 cited sources checked · 0 supported · 0 flagged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Surprisingly, the same stimulation had a much stronger impact on CA2 pyramidal neurons, generating somatic EPSPs up to 5 times larger than those in CA1 (Fig. 2A).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Reversed synaptic drive of EC versus CA3 inputs onto CA1 and CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“This is in contrast with the morphology of CA1 neurons, which have a main apical dendrite that either did not bifurcate within SR or bifurcated far from the soma (107.6 ± 11.1 μm, n = 14).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Characterization of CA2 pyramidal neurons
Strength:plain· not yet calibratedn = 14Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, the depolarizing sag in response to a hyperpolarizing current pulse, which is caused by the hyperpolarization-activated cation current (Ih), was much larger in CA1 neurons than in CA2 neurons (Fig. 1B and Table 1).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Characterization of CA2 pyramidal neurons
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, CA3 inputs onto proximal CA2 neuron dendrites are relatively weak, dominated by feed-forward inhibition, and fail to undergo LTP.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > INTRODUCTION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“As previously reported (Empson and Heinemann, 1995b), focal stimulation of the LIII EC axons (perforant path) in SLM elicited only very small EPSPs in the CA1 neuron soma, even with inhibitory transmission blocked by GABAA and GABAB receptor antagonists (Fig. 2A).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Reversed synaptic drive of EC versus CA3 inputs onto CA1 and CA2 pyramidal neurons
What the sources say
- Not checked yetcites Empson and Heinemann, 1995b
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, CA3 inputs onto proximal CA2 neuron dendrites are relatively weak, dominated by feed-forward inhibition, and fail to undergo LTP.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > INTRODUCTION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“CA2 neurons were further distinguished from CA1 neurons because the prominent slow after-hyperpolarization present in CA1 neurons was absent in CA2 neurons (Fig. 1A).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Characterization of CA2 pyramidal neurons
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, CA2 neurons make unusually strong unitary connections with CA1 neurons, forming a potent disynaptic circuit, independent of the trisynaptic path, that is powerfully regulated by long-term synaptic plasticity.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > INTRODUCTION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, CA2 neurons had a much larger soma than CA1 neurons (surface area of 391 ± 22 μm2 in CA2 versus 179 ± 11 μm2 in CA1).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Characterization of CA2 pyramidal neurons
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the IPSP (elicited by a 20 V stimulus) was −2.3 ± 0.4 mV in CA1 (n = 8) versus −3.7 ± 1.2 mV in CA2 (n = 8; p = 0.26; Fig. 2C).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Reversed synaptic drive of EC versus CA3 inputs onto CA1 and CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 51
- Probably not a substantial claim. 4
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the CA2 neuron input resistance was lower and the membrane capacitance was higher compared to CA1 or CA3 neurons (see Table 1).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Characterization of CA2 pyramidal neurons
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although LIII stimulation still evoked a large net depolarizing response in CA2 neurons, there was now often a net hyperpolarizing response observed in CA1 neurons (Fig. 2C).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Reversed synaptic drive of EC versus CA3 inputs onto CA1 and CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the apical dendrite bifurcated close to the soma (31.1 ± 3.6μm, n = 19) into two or three main branches that extended to stratum lacunosum moleculare (SLM) with few secondary, oblique branches in stratum radiatum (SR) but many branches in SLM (Fig. 1C and. Fig. S1).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Characterization of CA2 pyramidal neurons
Strength:plain· not yet calibratedn = 19Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the large CA2 EPSPs ensured the presence of a net depolarizing response even when inhibition was intact, with a 3–4 fold ratio of excitation to inhibition (Fig. 2D).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Reversed synaptic drive of EC versus CA3 inputs onto CA1 and CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The hyperpolarization in CA1 was not due to a lack of excitatory inputs as all CA1 neurons exhibited a clear EPSP in response to LIII stimulation in the presence of GABA blockers (n=24 out of 24 neurons).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Reversed synaptic drive of EC versus CA3 inputs onto CA1 and CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, whereas CA3 neurons fired a burst of action potentials at the beginning of a depolarizing current step, CA1 and CA2 neurons fired during the entire depolarization (Fig. 1A).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Characterization of CA2 pyramidal neurons
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stronger stimulation of LII inputs evoked a large inhibitory response, and addition of GABA blockers unmasked polysynaptic EPSPs (Fig. 5A).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LII and LIII EC neurons produce strong convergent excitation of CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Activation of LII inputs with a moderate stimulus produced surprisingly large EPSPs in CA2 neurons with little synaptic delay, indicating they were monosynaptic responses.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LII and LIII EC neurons produce strong convergent excitation of CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, SC stimulation never led to firing in CA2 (n = 0/8) but rather elicited a large net hyperpolarizing response (Fig. 4D,E).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LIII EC inputs drive firing in CA2 but not CA1 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Blocking inhibition greatly increased the efficiency of spike firing in CA1 neurons, with 100% of neurons firing spikes (11/11), and also enabled the SC inputs to trigger spikes in the majority of CA2 neurons (75%, n = 6/8, Fig. 4F).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LIII EC inputs drive firing in CA2 but not CA1 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As a result, SC stimulation produced a large net depolarization in CA1 neurons (EPSP/IPSP ratio ~2), whereas inhibition prevailed over excitation in CA2 (EPSP/IPSP < 1) (Fig. 3D).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Reversed synaptic drive of EC versus CA3 inputs onto CA1 and CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With inhibition intact, LIII stimulation produced a net hyperpolarization and failed to elicit a spike in CA1 neurons.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LIII EC inputs drive firing in CA2 but not CA1 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Following block of inhibition, the burst of LIII stimuli caused a larger depolarization that triggered spikes in 80% of CA2 neurons (n = 12/15) but remained subthreshold for nearly all CA1 neurons (only 1 in 12 fired a spike; Fig. 4C).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LIII EC inputs drive firing in CA2 but not CA1 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The induction of LTP at LIII synapses in both CA1 and CA2 was blocked by the NMDA receptor antagonist APV, indicating these two processes share certain molecular mechanisms (Fig. S3A).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Both LII and LIII synapses onto CA2 neurons express robust long-term potentiation
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although LII and LIII EC inputs to CA2 terminate in close proximity in SLM, LTP was pathway specific because LIII EC inputs displayed only a small and transient increase in efficacy when the HFS was delivered to LII EC inputs (Fig. S4C).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Both LII and LIII synapses onto CA2 neurons express robust long-term potentiation
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LTP at the LII –CA2 synapses was not altered in slices in which the mossy fiber inputs were cut, or with DCG-IV present to block glutamate release from the mossy fiber terminals, indicating that the LTP did not require activation of CA3 neurons (Fig. S4B).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Both LII and LIII synapses onto CA2 neurons express robust long-term potentiation
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We confirmed that the large LTP of the fEPSP was actually due to potentiation of synaptic responses in CA2 pyramidal neurons using whole cell recordings (Fig. S3B, 158.7 ± 5.2%, n = 6).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Both LII and LIII synapses onto CA2 neurons express robust long-term potentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Histograms of the EPSC amplitude distribution showed a prominent peak at 0 pA, representing the failures, and a broad distribution of EPSC successes clearly resolvable from the peak of failures.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Paired recordings demonstrate strong unitary CA2 CA1 synaptic connections
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Synaptic transmission at CA2–CA1 synapses is quantal.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When activated together, LII and LIII EPSPs showed linear summation for small amplitude EPSPs, whereas larger amplitude EPSPs displayed sublinear summation (Fig. 6A).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LII and LIII EC neurons produce strong convergent excitation of CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The LII EC synapses with CA2 neurons generated a correspondingly large LTP (194.3 ± 9.8% increase in the fEPSP, n = 6) that was more than two-fold greater than the amount of LTP at LII synapses in CA3 (135.1 ± 9.3%, n = 6, p = 0.0008, Fig. 7C).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Both LII and LIII synapses onto CA2 neurons express robust long-term potentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When stimulated at different intervals, the two inputs summated over a symmetrical time window that lasted around 20 ms and showed a maximum summation when activated simultaneously (Fig. 6B).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LII and LIII EC neurons produce strong convergent excitation of CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, induction of LTP at the LIII inputs produced a large, ~250% increase in the amplitude of the CA2 population spike elicited by strong stimulation (Fig. S4A), indicating an enhancement in the efficiency with which cortical inputs drive CA2 firing.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Both LII and LIII synapses onto CA2 neurons express robust long-term potentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The probability of a CA2–CA1 EPSC success ranged between 0.4 and 0.6 (Fig. 8D), similar to the value at CA3–CA1 synapses (Bolshakov and Siegelbaum, 1995).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Paired recordings demonstrate strong unitary CA2 CA1 synaptic connections
What the sources say
- Not checked yetcites Bolshakov and Siegelbaum, 1995
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Synaptic transmission at CA2–CA1 synapses is quantal.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, whereas a single peak of EPSC successes was reported for CA3–CA1 synapses, the CA2–CA1 EPSCs always showed multiple peaks of successes, which occurred at equally spaced intervals of around −5 pA (Fig. 8B).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Paired recordings demonstrate strong unitary CA2 CA1 synaptic connections
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Synaptic transmission at CA2–CA1 synapses is quantal.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“First, whereas CA1 neurons have a large number of oblique secondary dendrites in SR that shunt the synaptic current as it propagates down the dendrite, CA2 neurons have very few oblique dendrites in SR.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > Reversal of normal dendritic integration rules between CA1 and CA2 neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Excitatory synaptic inputs terminating on distal dendrites usually provide weaker somatic drive than proximal inputs due to cable properties.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although this residual hippocampal function was originally proposed to result from the ability of the direct connection from LIII EC neurons to drive the firing of CA1 neurons, such inputs generate weak EPSPs in the CA1 neuron soma, display little LTP, and recruit strong feed-forward inhibition that suppresses CA1 neuron output.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > Potential physiological role of CA2 neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we report that hippocampal CA2 pyramidal neurons, whose function has remained obscure for 75 years, have a reversed synaptic strength rule. Thus, CA2 neurons are strongly excited by their distal dendritic inputs from entorhinal cortex but only weakly activated by their more proximal dendritic inputs from hippocampal CA3 neurons.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“CA2 neurons could be further distinguished from CA3 neurons in that CA2 (and CA1) neuron dendrites branch along the transverse axis of the hippocampus (parallel to the plane of the slice) whereas CA3 neurons mostly extend their dendrites along the longitudinal axis of the hippocampus (Ishizuka et al., 1995).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Characterization of CA2 pyramidal neurons
What the sources say
- Not checked yetcites Ishizuka et al., 1995 source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this manner CA2 neurons form the nexus of a highly plastic disynaptic circuit linking the cortical input to the hippocampus to its CA1 neuronal ouput.”
- Also stated in: § INTRODUCTION · plain
“Finally, CA2 neurons make unusually strong unitary connections with CA1 neurons, forming a potent disynaptic circuit, independent of the trisynaptic path, that is powerfully regulated by long-term synaptic plasticity.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § INTRODUCTION · plain
None of the sources cited for this claim have been checked yet.
In the paper
“LII EC axons form excitatory synapses on granule cells in the molecular layer of dentate gyrus (DG), then project onto the distal dendrites of CA3 neurons, and finally terminate in a U shaped-area near the distal dendrites of CA2 (Niimi et al., 2007; Nishimura-Akiyoshi et al., 2007; Tamamaki and Nojyo, 1995).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LII and LIII EC neurons produce strong convergent excitation of CA2 pyramidal neurons
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that SC inputs on their own are strong enough to drive firing in CA2 pyramidal neurons, but their impact is tightly controlled by feed-forward inhibition.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LIII EC inputs drive firing in CA2 but not CA1 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The larger SC synaptic response in CA1 versus CA2 is consistent with the greater number of oblique dendritic branches in the SR of CA1 compared to CA2 neurons and the more extensive branching of CA3 axons in CA1 versus CA2, suggestive of a greater number of synaptic contacts.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Reversed synaptic drive of EC versus CA3 inputs onto CA1 and CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The larger SC intracellular EPSP in CA1 versus CA2 neurons is likely to result from a larger excitatory synaptic current as the local fEPSP in the SR region of CA1 was larger than that in CA2 (Fig. 3B), despite similar fiber volleys in both areas (not shown).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Reversed synaptic drive of EC versus CA3 inputs onto CA1 and CA2 pyramidal neurons
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“This polysynaptic response likely resulted from the recruitment of the DG→CA3→CA2 pathway either by activation of LII inputs to granule cells or by their direct activation as it was blocked by the mGluR-II agonist DCG-IV, which produces potent presynaptic inhibition at the mossy fiber synapses from DG to CA3 neurons but does not alter SC EPSPs (Kamiya et al., 1996) (Fig. 5A).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LII and LIII EC neurons produce strong convergent excitation of CA2 pyramidal neurons
What the sources say
- Not checked yetcites Kamiya et al., 1996 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“These data are consistent with the known anatomical projections of LII and LIII EC axons and confirm that our stimulating electrodes in DG and CA1 specifically recruited LII and LIII inputs, respectively.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LII and LIII EC neurons produce strong convergent excitation of CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Anatomical reconstructions have shown that CA2 pyramidal neurons send their axons to both SR and stratum oriens (SO) of CA1 (Tamamaki et al., 1988), whereas ipsilateral CA3 neurons only send their axons to SR.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > Paired recordings demonstrate strong unitary CA2 CA1 synaptic connections
What the sources say
- Not checked yetcites Tamamaki et al., 1988 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results show that both LII and LIII converge onto CA2 neurons where they interact and exert their maximal effect throughout the hippocampus.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > RESULTS > LII and LIII EC neurons produce strong convergent excitation of CA2 pyramidal neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Altogether, our findings in acute slices reveal that CA2 neurons are a major target of excitatory cortical input to the hippocampus and can potently excite their CA1 neuron targets.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First, CA2 neurons receive uniquely strong, convergent excitatory input from LII and LIII EC neurons, the only site of such convergence in the hippocampus.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Third, both the LII and LIII synapses with CA2 neurons undergo strong LTP, enhancing the efficacy with which these inputs fire CA2 neurons.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This inhibition is likely to be important in gating information flow between CA3 and CA2 and may explain why CA2 neurons do not normally mediate a significant quadrisynaptic loop from EC to DG to CA3 to CA2 to CA1.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > CA2 synaptic properties ensure independent disynaptic and trisynaptic hippocampal loops
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The relevance of this inhibitory drive is suggested by the findings that selective decreases in CA2 inhibition are associated with schizophrenia (Benes et al., 1998) and epilepsy (Williamson and Spencer, 1994), two pathological conditions in which hippocampal excitability is increased.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > CA2 synaptic properties ensure independent disynaptic and trisynaptic hippocampal loops
What the sources say
- Not checked yetcites Benes et al., 1998 source
- Not checked yetcites Williamson and Spencer, 1994
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The strong inhibition might also terminate CA2 neuron firing after its initial activation by the disynaptic loop, and thus prevent excessive activation of CA1 neurons.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > CA2 synaptic properties ensure independent disynaptic and trisynaptic hippocampal loops
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, the strong excitatory drive of the cortical inputs to CA2 neurons, combined with the unusually powerful unitary synaptic connection between CA2 and CA1 neurons, forms a robust disynaptic circuit that may be sufficient to drive CA1 neuron output to mediate key hippocampal functions in spatial learning and memory.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > CA2 synaptic properties ensure independent disynaptic and trisynaptic hippocampal loops
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Neurons were identified according to specific electrophysiological properties summarized in table 1.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > MATERIALS AND METHODS > Hippocampal slices
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, the EC inputs to CA2 neurons are strong and undergo robust LTP that enhances the excitatory drive of the disynaptic path.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > Potential physiological role of CA2 neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus the powerful excitatory disynaptic circuit linking EC to CA2 to CA1, combined with the marked feed-forward inhibition from CA3 to CA2, can explain how in vivo electrical stimulation of entorhinal cortex inputs leads to the initial firing of CA2 neurons, followed by firing of CA1 and then CA3 neurons (Bartesaghi and Gessi, 2004; Bartesaghi et al., 2006).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > Potential physiological role of CA2 neurons
What the sources say
- Not checked yetcites Bartesaghi and Gessi, 2004
- Not checked yetcites Bartesaghi et al., 2006 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Series resistance (typically 15–25 MΩ) was monitored throughout each experiment; cells with more than 15% change in series resistance were excluded from analysis.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > MATERIALS AND METHODS > Hippocampal slices
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The location of the recorded neurons in CA2 was subsequently confirmed after fixation of the slice for 1 hour in 4% paraformaldehyde in phosphate buffer (PBS). We further confirmed the location in CA2 by staining the slice for α-actinin 2, a protein enriched in the CA2 area (Wyszynski et al., 1998)”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > MATERIALS AND METHODS > Anatomical identification of CA2 pyramidal neurons
What the sources say
- Not checked yetcites Wyszynski et al., 1998 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“This excitation may actually be enhanced upon lesion of CA3 due to the loss of feed-forward inhibition, providing a potential explanation for the elevated rate of CA1 neuron place cell firing in the lesioned animals (Nakashiba et al., 2008).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > Potential physiological role of CA2 neurons
What the sources say
- Not checked yetcites Nakashiba et al., 2008 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Finally, CA2 neurons are the only hippocampal target of the supramammillary nucleus (which also targets the dentate gyrus), a structure involved in controlling the frequency of the theta rhythm (Pan and McNaughton, 2002) and the spread of epileptic activity (Saji et al., 2000) in the hippocampus.”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > Potential physiological role of CA2 neurons
What the sources say
- Not checked yetcites Pan and McNaughton, 2002
- Not checked yetcites Saji et al., 2000 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, the disynaptic circuit can account for the residual hippocampal-dependent memory and high levels of CA1 place cell firing in vivo following surgical or genetic lesions of CA3 (Brun et al., 2002; Nakashiba et al., 2008).”
§ Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop > DISCUSSION > Potential physiological role of CA2 neurons
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
CA2 pyramidal neuron function has remained obscure for 75 years.
“Here we report that hippocampal CA2 pyramidal neurons, whose function has remained obscure for 75 years, have a reversed synaptic strength rule.”
The paper relies on this without support.
The postsynaptic target of CA2 neurons has not been verified and a synaptic connection between CA2 and CA1 pyramidal neurons has never been reported.
“However, the postsynaptic target of CA2 neurons has not been verified and a synaptic connection between CA2 and CA1 pyramidal neurons has never been reported.”
The paper relies on this without support.
The CA2 region comprises a small population of neurons between CA3 and CA1.
“First characterized by (Lorente de No, 1934), the CA2 region comprises a small population of neurons between CA3 and CA1 whose function remains largely unexplored.”
The paper relies on this without support.
Most hippocampal neurons have weak unitary connections.
“Moreover, given the small number of CA2 neurons and the weak unitary connections between most hippocampal neurons, it is unclear how CA2 neuron input could elicit CA1 output.”
The paper relies on this without support.
Synaptic transmission at CA2–CA1 synapses is quantal.
“As expected for quantal synaptic transmission”
The paper relies on this without support.
Excitatory synaptic inputs terminating on distal dendrites usually provide weaker somatic drive than proximal inputs due to cable properties.
“Because of the cable properties of neuronal dendrites, excitatory synaptic inputs terminating on the distal regions of the dendritic tree usually provide a much weaker excitatory drive at the soma compared to inputs that terminate on more proximal regions of the dendritic tree.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“the electrophysiological properties of the YFP+ neurons differed significantly from those of CA1 PNs (Extended Data Table 1) and largely matched the values previously reported for CA2 pyramidal neurons7”
From The hippocampal CA2 region is essential for social memory (2014) · cites this paper as [7]
Citations
Cites
de Nó, R. L. (1934) · Cited by 1,974
The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.
Tsien, J. Z., Huerta, P. T., & Tonegawa, S. (1996) · Cell · doi:10.1016/s0092-8674(00)81827-9 · Cited by 1,782 · cited 1×
“Genetic approaches have demonstrated the importance of long-term potentiation of synaptic transmission (LTP) (Neves et al., 2008) at each stage of the trisynaptic circuit (McHugh et al., 2007; Otto et al., 2001; Tsien et al., 1996).”
Pyramidal neurons: dendritic structure and synaptic integration
Spruston, N. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2286 · Cited by 1,688
Synaptic plasticity, memory and the hippocampus: a neural network approach to causality
Neves, G., Cooke, S. F., & Bliss, T. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2303 · Cited by 1,287
The anatomy of memory: an interactive overview of the parahippocampal–hippocampal network
van Strien, N. M., Cappaert, N. L. M., & Witter, M. P. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2614 · Cited by 1,041
Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network
McHugh, T. J., Jones, M. W., Quinn, J. J., Balthasar, N., Coppari, R., Elmquist, J. K., Lowell, B. B., Fanselow, M. S., Wilson, M. A., & Tonegawa, S. (2007) · Science · doi:10.1126/science.1140263 · Cited by 958
Dendritic spikes as a mechanism for cooperative long-term potentiation
Golding, N. L., Staff, N. P., & Spruston, N. (2002) · Nature · doi:10.1038/nature00854 · Cited by 623
Dendritic Ih normalizes temporal summation in hippocampal CA1 neurons
Magee, J. C. (1999) · Nature Neuroscience · doi:10.1038/9158 · Cited by 617
Place cells and place recognition maintained by direct entorhinal-hippocampal circuitry
Brun, V. H., Otnæss, M. K., Molden, S., Steffenach, H.-A., Witter, M. P., Moser, M.-B., & Moser, E. I. (2002) · Science · doi:10.1126/science.1071089 · Cited by 606
Immunohistochemical localization of Ih channel subunits, HCN1–4, in the rat brain
Notomi, T., & Shigemoto, R. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.11039 · Cited by 558
Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning
Nakashiba, T., Young, J. Z., McHugh, T. J., Buhl, D. L., & Tonegawa, S. (2008) · Science · doi:10.1126/science.1151120 · Cited by 492
Hippocampus-independent phase precession in entorhinal grid cells
Hafting, T., Fyhn, M., Bonnevie, T., Moser, M., & Moser, E. I. (2008) · Nature · doi:10.1038/nature06957 · Cited by 485
A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives
Benes, F. M., Kwok, E. W., Vincent, S. L., & Todtenkopf, M. S. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00138-3 · Cited by 470
Impaired Spatial Representation in CA1 after Lesion of Direct Input from Entorhinal Cortex
Brun, V. H., Leutgeb, S., Wu, H., Schwarcz, R. M., Witter, M. P., Moser, E. I., & Moser, M. (2008) · Neuron · doi:10.1016/j.neuron.2007.11.034 · Cited by 382
Regulation of Hippocampal Transmitter Release During Development and Long-Term Potentiation
Bolshakov, V. Y., & Siegelbaum, S. A. (1995) · Science · doi:10.1126/science.7569903 · Cited by 375
Self-citationRole for a cortical input to hippocampal area CA1 in the consolidation of a long-term memory
Remondes, M., & Schuman, E. M. (2004) · Nature · doi:10.1038/nature02965 · Cited by 372
A quantitative analysis of the dendritic organization of pyramidal cells in the rat hippocampus
Ishizuka, N., Cowan, W. M., & Amaral, D. G. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903620103 · Cited by 350
Wouterlood, F. G., Saldana, E., & Witter, M. P. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.902960202 · Cited by 328
Kamiya, H., Shinozaki, H., & Yamamoto, C. (1996) · The Journal of Physiology · doi:10.1113/jphysiol.1996.sp021395 · Cited by 327
Pathway Interactions and Synaptic Plasticity in the Dendritic Tuft Regions of CA1 Pyramidal Neurons
Takahashi, H., & Magee, J. C. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.007 · Cited by 321
Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release
McMahon, H. T., Bolshakov, V. Y., Janz, R., Hammer, R. E., Siegelbaum, S. A., & Südhof, T. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4760 · Cited by 262
Self-citationTamamaki, N., & Nojyo, Y. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903530306 · Cited by 225
Young, W. S., Li, J., Wersinger, S. R., & Palkovits, M. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.040 · Cited by 222
Factors mediating powerful voltage attenuation along CA1 pyramidal neuron dendrites
Golding, N. L., Mickus, T. J., Katz, Y., Kath, W. L., & Spruston, N. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.086793 · Cited by 216
Regulation of HCN channel surface expression by a novel C-terminal protein-protein interaction
Santoro, B., Wainger, B. J., & Siegelbaum, S. A. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3300-04.2004 · Cited by 210
Self-citationDirect cortical input modulates plasticity and spiking in CA1 pyramidal neurons
Remondes, M., & Schuman, E. M. (2002) · Nature · doi:10.1038/416736a · Cited by 193
Otto, C., Kovalchuk, Y., Wolfer, D. P., Gass, P., Martin, M., Zuschratter, W., Gröne, H. J., Kellendonk, C., Tronche, F., Maldonado, R. J., et al. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-15-05520.2001 · Cited by 193
Dudman, J. T., Tsay, D., & Siegelbaum, S. A. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.020 · Cited by 192
Self-citationGeorge, M. S., Abbott, L. F., & Siegelbaum, S. A. (2009) · Nature Neuroscience · doi:10.1038/nn.2307 · Cited by 187
Self-citationSynaptic Plasticity (and the Lack Thereof) in Hippocampal CA2 Neurons
Zhao, M., Choi, Y., Obrietan, K. H., & Dudek, S. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4094-07.2007 · Cited by 181
Wyszynski, M., Kharazia, V., Shanghvi, R., Rao, A., Beggs, A. H., Craig, A. M., Weinberg, R., & Sheng, M. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-04-01383.1998 · Cited by 168
Empson, R. M., & Heinemann, U. (1995) · The Journal of Physiology · doi:10.1113/jphysiol.1995.sp020697 · Cited by 161
Tamamaki, N., Abe, K., & Nojyo, Y. (1988) · Brain Research · doi:10.1016/0006-8993(88)90030-3 · Cited by 156
Vasopressin 1b Receptor Knock-Out Impairs Memory for Temporal Order
DeVito, L. M., Konigsberg, R., Lykken, C., Sauvage, M., Young, W. S., & Eichenbaum, H. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5488-08.2009 · Cited by 147
Simons, S. B., Escobedo, Y., Yasuda, R., & Dudek, S. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904775106 · Cited by 134
Axonal netrin-Gs transneuronally determine lamina-specific subdendritic segments
Nishimura-Akiyoshi, S., Niimi, K., Nakashiba, T., & Itohara, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706919104 · Cited by 132
Characterization of Neurons in the CA2 Subfield of the Adult Rat Hippocampus
Mercer, A., Trigg, H. L., & Thomson, A. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1829-07.2007 · Cited by 113
Pan, W. X., & McNaughton, N. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02267.x · Cited by 112
Factors defining a pacemaker region for synchrony in the hippocampus
Wittner, L., & Miles, R. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.138131 · Cited by 81
Martig, A. K., & Mizumori, S. J. Y. (2010) · Hippocampus · doi:10.1002/hipo.20734 · Cited by 74
Delayed Signal Propagation via CA2 in Rat Hippocampal Slices Revealed by Optical Recording
Sekino, Y., Obata, K., Tanifuji, M., Mizuno, M., & Murayama, J. (1997) · Journal of Neurophysiology · doi:10.1152/jn.1997.78.3.1662 · Cited by 69
Parallel activation of field CA2 and dentate gyrus by synaptically elicited perforant path volleys
Bartesaghi, R., & GESSI, T. (2004) · Hippocampus · doi:10.1002/hipo.20011 · Cited by 59
Empson, R. M., & Heinemann, U. (1995) · Hippocampus · doi:10.1002/hipo.450050203 · Cited by 54
Bartesaghi, R., Migliore, M., & Gessi, T. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.06.001 · Cited by 54
Electrophysiological characterization of CA2 pyramidal cells from epileptic humans
Williamson, A., & Spencer, D. D. (1994) · Hippocampus · doi:10.1002/hipo.450040213 · Cited by 52
Levy, W. B., Desmond, N. L., & Zhang, D. X. (1998) · Learning & Memory · doi:10.1101/lm.4.6.510 · Cited by 43
Judge, S. J., & Hasselmo, M. E. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00848.2003 · Cited by 36
Saji, M., Kobayashi, S., Ohno, K., & Sekino, Y. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00081-6 · Cited by 20
Monoclonal antibodies discriminating netrin-G1 and netrin-G2 neuronal pathways
Niimi, K., Nishimura-Akiyoshi, S., Nakashiba, T., & Itohara, S. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2007.09.026 · Cited by 16
Samuel, W., Masliah, E., Brush, D. E., Garcia-Munoz, M., Patino, P., Young, S. J., & Groves, P. M. (1997) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1997.3789 · Cited by 12
Flagged first, then by citations
2 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The hippocampal CA2 region is essential for social memory
Hitti, F. L., & Siegelbaum, S. A. (2014) · Nature · doi:10.1038/nature13028 · Cited by 976
Self-citationCell type–specific genetic and optogenetic tools reveal hippocampal CA2 circuits
Kohara, K., Pignatelli, M., Rivest, A. J., Jung, H.-Y., Kitamura, T., Suh, J., Frank, D., Kajikawa, K., Mise, N., Obata, Y., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3614 · Cited by 528
Jackson, A. C., & Nicoll, R. A. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.007 · Cited by 410
Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling
Fernández‐Ruiz, A., Oliva, A., Nagy, G. A., Maurer, A. P., Berényi, A., & Buzsáki, G. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.017 · Cited by 344
Rediscovering area CA2: unique properties and functions
Dudek, S. M., Alexander, G. M., & Farris, S. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2015.22 · Cited by 333
Metadata
- Authors
- Chevaleyre, V., & Siegelbaum, S. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Chevaleyre, Vivien
- Siegelbaum, Steven A.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 66
- Issue
- 4
- Pages
- 560-572
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2905041
- OpenAlex
- W2079968698
- Semantic Scholar
- 74c42794d7b071743679598cdfc2c2006f247c7a
- Cited by
- 324
- References
- 52
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 18 · 2023: 27 · 2022: 24 · 2021: 27 · 2020: 21 · 2019: 20 · 2018: 29 · 2017: 20 · 2016: 21 · 2015: 14 · 2014: 17 · 2013: 15 · 2012: 12
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1209 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute (MH80745)
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- hippocampal CA2, pyramidal neurons, synaptic efficacy, entorhinal cortex, CA3, CA1, synaptic plasticity, spatial memory, hippocampal circuitry
- MeSH terms
- Animals, Cerebral Cortex, Mice, Inbred C57BL, Neural Pathways, Synapses, Pyramidal Cells, Mice, CA2 Region, Hippocampal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
