A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP

In the paper

“However, it is now clear that the Hebb rule does not account for late LTP; this requires an additional signal that is non-local.”

In the paper

“The opening of the NMDAR is Hebbian: the channel opens only if there is both presynaptic glutamate release and strong postsynaptic depolarization.”

In the paper

“In primates, novel stimuli can trigger burst firing of dopamine cells which habituates as stimuli become familiar [44].”

What the sources say

• Not checked yetcites [44] Ljungberg T 1992 Responses of monkey dopamine neurons during learning of behavioral reactions J Neurophysiol 67 145 163 1552316 source

In the paper

“Furthermore, preventing strong depolarization by injecting negative current prevents the induction of LTP [4].”

What the sources say

• Not checked yetcites [4] Malinow R Miller JP 1986 Postsynaptic hyperpolarization during conditioning reversibly blocks induction of long-term potentiation Nature 320 529 530 3008000

In the paper

“Whereas the Hebbian NMDAR-dependent processes in the slice occur only during the initial induction of LTP, events in vivo also involve NMDAR-dependent processes triggered by hippocampal replay processes [142].”

What the sources say

• Not checked yetcites [142] Shimizu E 2000 NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation Science (New York, N Y 290 1170 1174 11073458

In the paper

“the observation that novelty-related activation of the SN/VTA has a long (ca. 30 minutes) penumbra that affects memory for unrelated information (e.g. exposure to novel scenes can affect memory for words) [74]”

What the sources say

• Not checked yetcites [74] Fenker DB 2008 Novel scenes improve recollection and recall of words J Cogn Neurosci 20 1250 1265 18284351

In the paper

“Based on these results, one would predict that dopamine antagonists would produce a weak reduction of memory at short times after learning but would produce a strong reduction at later times.”

In the paper

“Early experiments revealed that dopamine antagonists applied during the LTP induced by multiple tetani (generally 100Hz for 1s) had an effect that was strongly time dependent [7]. Whereas the first phase of LTP was not strongly affected, the potentiation measured an hour after induction was strongly attenuated.”

What the sources say

• Not checked yetcites [7] Frey U 1990 Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the CA1 region of rat hippocampal slices Brain research 522 69 75 1977494

In the paper

“Another quandary was posed by early work showing that dopamine agonists alone could produce potentiation [21].”

What the sources say

• Not checked yetcites [21] Huang YY Kandel ER 1995 D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus Proceedings of the National Academy of Sciences of the United States of America 92 2446 2450 7708662 PMC42234

In the paper

“Results such as those shown in Fig. 1 (top traces) suggest that early LTP is completely unaffected by dopamine antagonist.”

In the paper

“Late LTP is blocked by D1 antagonists [14] (Fig. 1A) and by genetic deletion of D1 receptors (Fig. 1C) [15, 16].”

What the sources say

• Not checked yetcites [14] O’Carroll CM Morris RG 2004 Heterosynaptic co-activation of glutamatergic and dopaminergic afferents is required to induce persistent long-term potentiation Neuropharmacology 47 324 332 15275821
• Not checked yetcites [15] Matthies H 1997 Dopamine D1-deficient mutant mice do not express the late phase of hippocampal long-term potentiation Neuroreport 8 3533 3535 9427321
• Not checked yetcites [16] Granado N 2008 D1 but not D5 dopamine receptors are critical for LTP, spatial learning, and LTP-Induced arc and zif268 expression in the hippocampus Cereb Cortex 18 1 12 17395606

In the paper

“Thus, although 89% of VTA dopaminergic neurons respond with activation to a conditioned reward, they also respond to fearful events, with the majority of the neurons showing suppression. Interestingly, 25% respond with excitation to both positive and fearful events [101].”

What the sources say

• Not checked yetcites [101] Wang DV Tsien JZ 2011 Convergent processing of both positive and negative motivational signals by the VTA dopamine neuronal populations PloS one 6 e17047 21347237 PMC3039659 source

In the paper

“LTP at these later times (termed late LTP) is dependent on protein synthesis, whereas the LTP at early times is not [13].”

What the sources say

• Not checked yetcites [13] Frey U 1993 Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons Science (New York, N Y 260 1661 1664 8389057 source

In the paper

“It is now well-established that dopamine neurons can also fire in response to unexpected aversive outcomes and cues predicting punishments [45].”

What the sources say

• Not checked yetcites [45] Bromberg-Martin ES 2010 Dopamine in motivational control: rewarding, aversive, and alerting Neuron 68 815 834 21144997 PMC3032992 source

In the paper

“Thus, both early and late LTP are dopamine-dependent, but late LTP has a stronger dependence.”

In the paper

“Furthermore, depletion of dopamine selectively blocks late LTP [18], a block that can be reversed by a D1 agonist (Fig. 1D).”

What the sources say

• Not checked yetcites [18] Yang HW 2002 Change in bi-directional plasticity at CA1 synapses in hippocampal slices taken from 6-hydroxydopamine-treated rats: the role of endogenous norepinephrine The European journal of neuroscience 16 1117 1128 12383241

In the paper

“This one-trial memory for novel associations is critically dependent on the hippocampus and on glutamatergic neurotransmission during encoding [25, 26].”

What the sources say

• Not checked yetcites [25] Tse D 2007 Schemas and memory consolidation Science (New York, N Y 316 76 82 17412951 source
• Not checked yetcites [26] Bethus I 2010 Dopamine and memory: modulation of the persistence of memory for novel hippocampal NMDA receptor-dependent paired associates J Neurosci 30 1610 1618 20130171 PMC6633999 source

In the paper

“In reinforcement learning, dopamine responses conform with a signed prediction error; they increase for better than expected (reward) outcomes and decrease for worse than expected (aversive) outcomes [43].”

What the sources say

• Not checked yetcites [43] Schultz W 2007 Multiple dopamine functions at different time courses Annual review of neuroscience 30 259 288 17600522 source

In the paper

“Reward-related SN/VTA activation improves memory for the rewarded stimulus, but not for the non-rewarded stimuli given in close temporal proximity [57]”

What the sources say

• Not checked yetcites [57] Wittmann B 2011 Behavioural specifications of reward-associated long-term memory enhancement in humans Learning and Memory 18 296 300 21502336 PMC3465832

In the paper

“Thus, it is now clear that dopamine by itself does not produce potentiation; rather, it acts as a permissive signal for the late-phase LTP induced by a NMDAR-dependent process.”

In the paper

“In monkeys, a substantial fraction of dopamine neurons in the dorsolateral SN/VTA are responsive to conditioned cues predicting aversive events; in contrast, those in the more ventromedial portions of the SN/VTA are inhibited by aversive stimuli [97]”

What the sources say

• Not checked yetcites [97] Matsumoto M Hikosaka O 2009 Two types of dopamine neuron distinctly convey positive and negative motivational signals Nature 459 837 841 19448610 PMC2739096 source

In the paper

“However, it was subsequently shown that this potentiation depended on the action of test pulses given during agonist application and that activation of NMDARs by the test pulses was required [22].”

What the sources say

• Not checked yetcites [22] Navakkode S 2007 Synergistic requirements for the induction of dopaminergic D1/D5-receptor-mediated LTP in hippocampal slices of rat CA1 in vitro Neuropharmacology 52 1547 1554 17433377

In the paper

“In vivo recordings show that CA3/CA1 synapses are strengthened over time during trace eyeblink conditioning but that this strengthening is greatly reduced either in D1 receptor knockout mice or after reducing D1 receptors by virally delivered siRNA [16].”

What the sources say

• Not checked yetcites [16] Granado N 2008 D1 but not D5 dopamine receptors are critical for LTP, spatial learning, and LTP-Induced arc and zif268 expression in the hippocampus Cereb Cortex 18 1 12 17395606

In the paper

“Intrahippocampal infusion of the D1/D5 dopaminergic antagonist SCH23390 just before encoding causes impaired memory for the new reward-location association measured 24 hours later, but has no effect on early memory measured at 30 minutes [26]”

What the sources say

• Not checked yetcites [26] Bethus I 2010 Dopamine and memory: modulation of the persistence of memory for novel hippocampal NMDA receptor-dependent paired associates J Neurosci 30 1610 1618 20130171 PMC6633999 source

In the paper

“Although the SN and VTA are known as dopaminergic regions, some cells in these regions are GABAergic or glutamatergic, and others release both glutamate and dopamine [31, 32].”

What the sources say

• Not checked yetcites [31] Nair-Roberts RG 2008 Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat Neuroscience 152 1024 1031 18355970 PMC2575227
• Not checked yetcites [32] Hnasko TS 2010 Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo Neuron 65 643 656 20223200 PMC2846457 source

In the paper

“Studies performed both in vivo and in vitro show that the tonic mode is driven by intrinsic pacemaker conductances [34, 36].”

What the sources say

• Not checked yetcites [34] Grace AA Bunney BS 1983 Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--1. Identification and characterization Neuroscience 10 301 315 6633863
• Not checked yetcites [36] Grace AA Onn SP 1989 Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro J Neurosci 9 3463 3481 2795134 PMC6569889

In the paper

“Activation of the ventral subiculum (an output structure of the hippocampus) excites the nucleus accumbens (Nac), which, in turn, inhibits the ventral pallidum. This reduces the inhibition of dopamine cells and thereby increases the number of tonically firing cells [38, 39].”

What the sources say

• Not checked yetcites [38] Floresco SB 2001 Glutamatergic afferents from the hippocampus to the nucleus accumbens regulate activity of ventral tegmental area dopamine neurons Journal of Neuroscience 21 4915 4922 11425919 PMC6762358
• Not checked yetcites [39] Floresco SB 2003 Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission Nature neuroscience 6 968 973 12897785

In the paper

“These results indicate that burst firing controls some downstream functions, but others may depend on how many cells are in the tonic mode (see Boxes 3 and 4).”

In the paper

“Thus, novelty, reward stimuli and aversive stimuli are all able to activate the dopamine system in both monkeys and humans.”

In the paper

“The perirhinal cortex [65], for instance, shows much stronger responses to novel items than familiar items and may form connects to the PPTg (Figure I), a structure that regulates the SN/VTA.”

What the sources say

• Not checked yetcites [65] Xiang JZ Brown MW 1998 Differential neuronal encoding of novelty, familiarity and recency in regions of the anterior temporal lobe Neuropharmacology 37 657 676 9705004

In the paper

“Classical work showed the importance of reward as a stimulus for the bursting of these cells [43]”

What the sources say

• Not checked yetcites [43] Schultz W 2007 Multiple dopamine functions at different time courses Annual review of neuroscience 30 259 288 17600522 source

In the paper

“selective genetic inactivation of NMDARs in dopaminergic cells blocked burst production and prevented conditioned behavioral responses that were dependent on dopamine [41]”

What the sources say

• Not checked yetcites [41] Zweifel LS 2009 Disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of phasic dopamine-dependent behavior Proceedings of the National Academy of Sciences of the United States of America 106 7281 7288 19342487 PMC2678650 source

In the paper

“Other work using fMRI has demonstrated that activation can also occur due to aversive events [53] as well as novel stimuli [54].”

What the sources say

• Not checked yetcites [53] Guitart-Masip M 2011 Action dominates valence in anticipatory representations in the human striatum and dopaminergic midbrain Journal of Neuroscience 31 7867 7875 21613500 PMC3109549
• Not checked yetcites [54] Duzel E 2010 NOvelty-related motivation of anticipation and exploration by dopamine (NOMAD): implications for healthy aging Neuroscience and biobehavioral reviews 34 660 669 19715723 source

In the paper

“Midbrain dopamine neurons consist of three largely contiguous cell groups: the retrorubral field (cell group A8 in the rat nomenclature), the substantia nigra pars compacta (SNc, A9), and the ventral tegmental area (VTA, A10) [28, 29].”

What the sources say

• Not checked yetcites [28] Dahlström A Fuxe K 1964 Evidence for the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons Acta Physiol Scand 62 1 80 14229500
• Not checked yetcites [29] Beckstead RM 1979 Efferent connections of the substantia nigra and ventral tegmental area in the rat Brain research 175 191 217 314832 source

In the paper

“Furthermore, this improvement should be small with short delays when early LTP is present, but large at much longer delays when late LTP is present.”

In the paper

“More recent work has demonstrated conditions under which dopamine cells can be driven by aversive stimuli (reviewed in [45]; see also Box 2).”

What the sources say

• Not checked yetcites [45] Bromberg-Martin ES 2010 Dopamine in motivational control: rewarding, aversive, and alerting Neuron 68 815 834 21144997 PMC3032992 source

In the paper

“Dopamine has no effect on the previously formed memories and is not required at the time of retrieval [27].”

What the sources say

• Not checked yetcites [27] O’Carroll CM 2006 Dopaminergic modulation of the persistence of one-trial hippocampus-dependent memory Learning & memory (Cold Spring Harbor, N Y 13 760 769 PMC1783630 17142305

In the paper

“These data demonstrate that D1/D5 receptor-mediated effects do not strongly affect encoding or early memory, but do affect memory at later times.”

In the paper

“However, in the absence of an expected reward, or if a worse than expected outcome occurs (i.e., a negative prediction error), the consequent depression of dopaminergic neuron activity would attenuate dopamine-mediated potentiation of the ventral subiculum while at the same time removing inhibition of the mPFC input. Consequently the mPFC would drive the animal to switch response strategies [122].”

What the sources say

• Not checked yetcites [122] Goto Y Grace AA 2008 Limbic and cortical information processing in the nucleus accumbens Trends in neurosciences 31 552 558 18786735 PMC2884964

In the paper

“In a condition in which the animal’s behavior leads to a better than expected outcome and phasic release (i.e. positive prediction error), the subicular input would be potentiated, causing the animal to maintain focus on the current task, thus allowing rewarded behaviors to be maintained.”

In the paper

“while subsequent studies have demonstrated that a novel stimulus (in the absence of reward) can also produce burst firing [44].”

What the sources say

• Not checked yetcites [44] Ljungberg T 1992 Responses of monkey dopamine neurons during learning of behavioral reactions J Neurophysiol 67 145 163 1552316 source

In the paper

“The lateral habenula provides SN/VTA dopamine neurons with a negative reward-prediction signal through the fasciculus retroflexus fiber bundles [[119]].”

What the sources say

• Not checked yetcites [119] Matsumoto M Hikosaka O 2007 Lateral habenula as a source of negative reward signals in dopamine neurons Nature 447 1111 1115 17522629 source

In the paper

“Frey and Morris propose that this specificity occurs because LTP immediately produces a synapse-specific “tag” and that PRPs can only produce late LTP at tagged synapses.”

What the sources say

• Not checked yetcites [9] Frey U Morris RG 1997 Synaptic tagging and long-term potentiation [see comments] Nature 385 533 536 9020359

In the paper

“The hippocampus, on the other hand, integrates information about stimuli and their spatial location into a contextual representation and can compute various types of novel changes in these relationships.”

In the paper

“Indeed, fMRI studies (for examples see Box 2 Figure 1) confirm SN/VTA activation by associative novelty [60] and stimulus novelty [61] but less by other salient events such as rareness or negative emotional content [61].”

What the sources say

• Not checked yetcites [60] Schott BH 2004 Activation of midbrain structures by associative novelty and the formation of explicit memory in humans Learning & memory (Cold Spring Harbor, N Y 11 383 387 15254215
• Not checked yetcites [61] Bunzeck N Duzel E 2006 Absolute stimulus-novelty is coded by the human substantia nigra/VTA Neuron 3 369 379 16880131 source

In the paper

“positron emission tomography (PET) studies in humans show that novelty-seeking traits are inversely associated with D2-like receptor availability in the SN/VTA region [62] and are positively correlated with white matter connectivity between the hippocampus and the ventral striatum [63].”

What the sources say

• Not checked yetcites [62] Zald DH 2008 Midbrain dopamine receptor availability is inversely associated with novelty-seeking traits in humans J Neurosci 28 14372 14378 19118170 PMC2748420
• Not checked yetcites [63] Cohen MX 2009 Connectivity-based segregation of the human striatum predicts personality characteristics Nature neuroscience 12 32 34 19029888

In the paper

“From the perspective of the neoHebbian framework, this negative result is understandable; i.e., the SN/VTA activity-related enhancement of memory would be more apparent if testing is conducted after long retention intervals.”

In the paper

“In the perirhinal cortex, for instance, stimulus-related incoming information can be compared to stored information and a stimulus-related novelty signal is computed [65].”

What the sources say

• Not checked yetcites [65] Xiang JZ Brown MW 1998 Differential neuronal encoding of novelty, familiarity and recency in regions of the anterior temporal lobe Neuropharmacology 37 657 676 9705004

In the paper

“The human SN/VTA is also activated by cues that predict novel images, or by unexpected novel images that followed familiarity-predictive cues (ie. an ‘unexpected novelty’ response) [64].”

What the sources say

• Not checked yetcites [64] Wittmann BC 2007 Anticipation of novelty recruits reward system and hippocampus while promoting recollection Neuroimage 38 194 202 17764976 PMC2706325

In the paper

“Moreover, other properties of LTP (weak/strong; penumbra) appear also to have predictive power in explaining properties of memory.”

In the paper

“In schizophrenia, the enhanced activation of the hippocampal system may increase dopamine release and skew behavioral choice towards repetitive behavior (see Box 3).”

What the sources say

• Not checked yetcites Box 3

In the paper

“That this drug-induced memory impairment is not due to an effect of dopamine on encoding is nicely demonstrated by the rescue of long-term memory if there is a preceding exposure to a novel environment [72].”

What the sources say

• Not checked yetcites [72] Wang SH 2010 Relevance of synaptic tagging and capture to the persistence of long-term potentiation and everyday spatial memory Proceedings of the National Academy of Sciences of the United States of America 107 19537 19542 20962282 PMC2984182

In the paper

“Parkinson’s disease (PD) usually begins with loss of nigrostriatal dopamine cells in the ventral tier SNc, leaving the dorsal tier projection neurons to the hippocampus, ventral striatum, and cortex intact [79].”

What the sources say

• Not checked yetcites [79] Fearnley JM Lees AJ 1991 Ageing and Parkinson’s disease: substantia nigra regional selectivity Brain 114 Pt 5 2283 2301 1933245 source

In the paper

“long-term retention is not helped by simple re-exposure to recently learned material but is greatly helped by retesting even when subjects already know the answer [83].”

What the sources say

• Not checked yetcites [83] Karpicke JD Roediger HL 3rd 2008 The critical importance of retrieval for learning Science (New York, N Y 319 966 968 18276894 source

In the paper

“a single exposure to the location of a small reward is rapidly forgotten in rodents within a few hours, but persists for at least 24 hours if it is preceded or followed (within 30 minutes) by novelty exploration [72].”

What the sources say

• Not checked yetcites [72] Wang SH 2010 Relevance of synaptic tagging and capture to the persistence of long-term potentiation and everyday spatial memory Proceedings of the National Academy of Sciences of the United States of America 107 19537 19542 20962282 PMC2984182

In the paper

“It appears that both the tag and the PRPs have considerable lifetimes.”

In the paper

“stimulation of protein synthesis and the induction of Hebbian plasticity do not need to be coincident; indeed, the trigger for protein synthesis can occur either before or after Hebbian plasticity (with intervening periods of many minutes).”

In the paper

“A key insight to emerge from physiological experiments is that LTP at short times is relatively insensitive to dopamine, whereas LTP with longer delays is sensitive.”