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

Gene-targeted mice lacking the l -α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A ^−/− mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca ²⁺ transients, Ca ²⁺ -dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A ^−/− mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.

The three-dimensional morphology of the axosomatic synaptic structures between a calyx of Held and a principal neuron in the medial nucleus of the trapezoid body (MNTB) in the brainstem of young postnatal day 9 rats was reconstructed from serial ultrathin sections. In the apposition zone between the calyx and the principal neuron two types of membrane specializations were identified: synaptic contacts (SCs) with active zones (AZs) and their associated postsynaptic densities (PSDs) constituted ∼35% (n = 554) of the specializations; the remaining 65% (n = 1010) were puncta adherentia (PA). Synaptic contacts comprised ∼5% of the apposition area of presynaptic and postsynaptic membranes. A SC had an average area of 0.100 μm², and the nearest neighbors were separated, on average, by 0.59 μm. Approximately one-half of the synaptic vesicles in the calyx were clustered within a distance of 200 nm of the AZ membrane area, a cluster consisting of ∼60 synaptic vesicles (n = 52 SCs). Approximately two synaptic vesicles per SC were “anatomically docked.” Comparing the geometry of the synaptic structure with its previously studied functional properties, we find that during a single presynaptic action potential (AP) (1) ∼35% of the AZs release a transmitter quantum, (2) the number of SCs and anatomically docked vesicles is comparable with the low estimates of the readily releasable pool (RRP) of quanta, and (3) the broad distribution of PSD areas [coefficient of variation (CV) = 0.9] is likely to contribute to the large variability of miniature EPSC peaks. The geometry of the reconstructed synapse suggests that each of the hundreds of SCs is likely to contribute independently to the size and rising phase of the EPSC during a single AP.