Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex.
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1. Dual voltage recordings were made from pairs of adjacent, synaptically connected thick tufted layer 5 pyramidal neurones in brain slices of young rat (14‐16 days) somatosensory cortex to examine the physiological properties of unitary EPSPs. Pre‐ and postsynaptic neurones were filled with biocytin and examined in the light and electron microscope to quantify the morphology of axonal and dendritic arbors and the number and location of synaptic contacts on the target neurone. 2. In 138 synaptic connections between pairs of pyramidal neurones 96 (70%) were unidirectional and 42 (30%) were bidirectional. The probability of finding a synaptic connection in dual recordings was 0.1. Unitary EPSPs evoked by a single presynaptic action potential (AP) had a mean peak amplitude ranging from 0.15 to 5.5 mV in different connections with a mean of 1.3 +/‐ 1.1 mV, a latency of 1.7 +/‐ 0.9 ms, a 20‐80% rise time of 2.9 +/‐ 2.3 ms and a decay time constant of 40 +/‐ 18 ms at 32‐24 degrees C and ‐60 +/‐ 2 mV membrane potential. 3. Peak amplitudes of unitary EPSPs fluctuated randomly from trial to trial. The coefficient of variation (c.v.) of the unitary EPSP amplitudes ranged from 0.13 to 2.8 in different synaptic connections (mean, 0.52; median, 0.41). The percentage of failures of single APs to evoke a unitary EPSP ranged from 0 to 73% (mean, 14%; median, 7%). Both c.v. and percentage of failures decreased with increasing mean EPSP amplitude. 4. Postsynaptic glutamate receptors which mediate unitary EPSPs at ‐60 mV were predominantly of the L‐alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor type. Receptors of the N‐methyl‐D‐aspartate (NMDA) type contributed only a small fraction (< 20%) to the voltage‐time integral of the unitary EPSP at ‐60 mV, but their contribution increased at more positive membrane potentials. 5. Branching patterns of dendrites and axon collaterals of forty‐five synaptically connected neurones, when examined in the light microscope, indicated that the axonal and dendritic anatomy of both projecting and target neurones and of uni‐ and bidirectionally connected neurones was uniform. 6. The number of potential synaptic contacts formed by a presynaptic neurone on a target neurone varied between four and eight (mean, 5.5 +/‐ 1.1 contacts; n = 19 connections). Synaptic contacts were preferentially located on basal dendrites (63%, 82 +/‐ 35 microns from the soma, n = 67) and apical oblique dendrites (27%, 145 +/‐ 59 microns, n = 29), and 35% of all contacts were located on tertiary basal dendritic branches. The mean geometric distances (from the soma) of the contacts of a connection varied between 80 and 585 microns (mean, 147 microns; median, 105 microns). The correlation between EPSP amplitude and the number of morphologically determined synaptic contacts or the mean geometric distances from the soma was only weak (correlation coefficients were 0.2 and 0.26, respectively). 7. Compartmental models constructed from camera lucida drawings of eight target neurones showed that synaptic contacts were located at mean electrotonic distances between 0.07 and 0.33 from the soma (mean, 0.13). Simulations of unitary EPSPs, assuming quantal conductance changes with fast rise time and short duration, indicated that amplitudes of quantal EPSPs at the soma were attenuated, on average, to < 10% of dendritic EPSPs and varied in amplitude up to 10‐fold depending on the dendritic location of synaptic contacts. The inferred quantal peak conductance increase varied between 1.5 and 5.5 nS (mean, 3 nS). 8. The combined physiological and morphological measurements in conjunction with EPSP simulations indicated that the 20‐fold range in efficacy of the synaptic connections between thick tufted pyramidal neurones, which have their synaptic contacts preferentially located on basal and apical oblique dendrites, was due to differences in transmitter release probability of the projecting neurones and, to a lesser extent, to differenc
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Synaptic connections of axons that arise within the same cortical column in the neocortex preferentially innervate the proximal basal dendrites of pyramidal cells.
“For example, the synaptic connections of axons that arise within the same cortical column in the neocortex preferentially innervate the proximal basal dendrites of pyramidal cells (Markram et al., 1997; Feldmeyer et al., 2002).”
From The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease (2013) · cites this paper as Markram et al., 1997
The proximal and distal segments of basal dendrites have different characteristics with respect to integration and synaptic plasticity.
“Moreover, the proximal and distal segments of basal dendrites have different characteristics with respect to integration and synaptic plasticity (Markram et al., 1997; Hausser and Mel, 2003; Gordon et al., 2006; Gelfo et al., 2009; Branco and Häusser, 2011).”
From The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease (2013) · cites this paper as Markram et al., 1997
Tissue shrinkage due to the fixation and staining procedures was about 10-20%.
“Consistently with previous studies, tissue shrinkage due to the fixation and staining procedures was about 10–20%5,28,49.”
From Phenotypic variation of transcriptomic cell types in mouse motor cortex (2021) · cites this paper as [49]
The connection probability between pyramidal neurons in V1 L4 was very low, consistent with previous work in other layers in adult animals but in contrast to findings in young and juvenile rodents.
“Notably, the connection probability between PYRs in V1 L4 was very low, consistent with our previous work in other layers in adult animals29, but in contrast to the findings in young and juvenile rodents51,52.”
From Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas (2019) · cites this paper as [51]
Tissue shrinkage due to fixation and staining was about 10-20%, consistent with previous studies.
“Tissue shrinkage due to the fixation and staining procedures was about 10–20%, consistent with previous studies29,51.”
From Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas (2019) · cites this paper as [51]
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- Authors
- Markram, H., Lübke, J., Frotscher, M., Roth, A., & Sakmann, B.
- Affiliations
- Max Planck Society (DE)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 1997-04-15
- Volume
- 500
- Issue
- 2
- Pages
- 409-440
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC1159394
- OpenAlex
- W1976738367
- Cited by
- 960
- References
- 47
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 31 · 2023: 22 · 2022: 27 · 2021: 24 · 2020: 25 · 2019: 37 · 2018: 32 · 2017: 37 · 2016: 29 · 2015: 50 · 2014: 39 · 2013: 46 · 2012: 41
- FWCI
- 10.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- synaptic connectivity, layer 5 pyramidal neurons, somatosensory cortex, synaptic plasticity, synaptic depression, synaptic facilitation, AMPA receptors, NMDA receptor, glutamate receptors, dendritic branching, axon branching, synaptic asymmetry, rat neocortex, presynaptic inhibition
- MeSH terms
- Action Potentials, Animals, Cerebral Cortex, Dendrites, Electric Conductivity, Electric Stimulation, Microscopy, Interference, Synaptic Transmission, Synapses, Time Factors, Ion Channel Gating, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Pyramidal Cells, Receptors, AMPA, Patch-Clamp Techniques, Microscopy, Video, Cell Size, Rats
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