Synaptic output of individual layer 4 neurons in guinea pig visual cortex

More than 90% of geniculocortical axons from the dorsal lateral geniculate nucleus of the thalamus innervate layer 4 (L4) of V1 (primary visual cortex). Excitatory neurons, which comprise >80% of the neuronal population in L4, synapse mainly onto adjacent L4 neurons and layer 2/3 (L2/3) neurons. It has been suggested that intralaminar L4-L4 connections contribute to amplifying and refining thalamocortical signals before routing to L2/3. To unambiguously probe the properties of the synaptic outputs from these L4 excitatory neurons, we used multiple simultaneous whole-cell patch-clamp recording and stimulation from two to four neighboring L4 neurons. We recorded uEPSCs (evoked unitary synaptic currents) in response to pairs of action potentials elicited in single presynaptic L4 neurons for 102 L4 cell pairs and found that their properties are more diverse than previously described. Averaged unitary synaptic response peak amplitudes spanned almost three orders of magnitude, from 0.42 to 192.92 pA. Although connections were, on average, reliable (average failure rate, 25%), we recorded a previously unknown subset of unreliable (failure rates from 30 to 100%) and weak (averaged response amplitudes, <5 pA) connections. Reliable connections with high probability of neurotransmitter release responded to paired presynaptic pulses with depression, whereas unreliable connections underwent paired-pulse facilitation. Recordings from interconnected sets of L4 triplets revealed that synaptic response amplitudes and reliability were equally variable between independent cell pairs and those that shared a common presynaptic or postsynaptic cell, suggesting local perisynaptic influences on the development and/or state of synaptic function.