Layer 6 cortico-thalamic pyramidal cells preferentially innervate interneurons and generate facilitating EPSPs.

The properties of the connections made by the axons of pyramidal cells with cortico-thalamic (CT)-like morphology with a range of postsynaptic layer 6 targets were studied with dual intracellular recordings in slices of adult rat and cat neocortex. The cells were filled with biocytin and identified morphologically and, where appropriate, immunofluorescently. CT-like pyramids contacted interneurons with a very high probability (up to 1:2) but contacted other layer 6 pyramidal cells only rarely (approximately 1:80). The excitatory postsynaptic potentials (EPSPs) that they elicited both in pyramidal cells and in a variety of types of interneurons (including those immunopositive for parvalbumin and for somatostatin) facilitated, the second EPSP being larger than the first over a range of interspike intervals. Facilitation was not, however, maximal at the shortest intervals; in fact, depression was apparent at some connections at short interspike intervals. Facilitation in the majority of connections peaked at intervals of 25-35 ms and then declined slowly. Nor did these connections display the augmentation typical of many other strongly facilitating connections. Third EPSPs were smaller on average than second EPSPs, and fourth and subsequent EPSPs could be depressed (relative to first EPSPs). The properties of the outputs of these CT-like pyramidal cells are therefore quite distinct from those of other pyramidal cells, both within layer 6 and in other layers, possibly reflecting their unique role as both first order thalamo-cortical recipient and cortico-thalamic output neurons.

Excitatory connections made by presynaptic cortico-cortical pyramidal cells in layer 6 of the neocortex.

Paired intracellular recordings with biocytin labelling were made in slices of adult rat somatosensory and visual cortex and in cat visual cortex to examine the properties of synaptic connections made by layer 6 pyramidal cells, to determine whether cortico-cortical pyramids more commonly provide input to other layer 6 pyramids than cortico-thalamic cells, and whether these connections exhibit paired pulse and brief train depression. Pyramidal cells with cortico-cortical like morphology were 2-4 times more likely to innervate other pyramidal cells than were cortico-thalamic like cells, but less likely to innervate inhibitory interneurons. The excitatory postsynaptic potentials elicited by presynaptic, phasically firing cortico-cortical pyramids in all classes of postsynaptic infragranular layer pyramidal cells exhibited strong, presynaptically mediated paired pulse and brief train depression. Those with larger paired pulse ratios also exhibited post-tetanic potentiation, but this was accompanied by stronger paired pulse and brief train depression. Both the firing characteristics and the outputs of cortico-cortical pyramidal cells display pronounced phasic characteristics, indicating that these cells respond most effectively to and preferentially pass on information related to novelty.

Target and temporal pattern selection at neocortical synapses.

We attempt to summarize the properties of cortical synaptic connections and the precision with which they select their targets in the context of information processing in cortical circuits. High-frequency presynaptic bursts result in rapidly depressing responses at most inputs onto spiny cells and onto some interneurons. These 'phasic' connections detect novelty and changes in the firing rate, but report frequency of maintained activity poorly. By contrast, facilitating inputs to interneurons that target dendrites produce little or no response at low frequencies, but a facilitating-augmenting response to maintained firing. The neurons activated, the cells they in turn target and the properties of those synapses determine which parts of the circuit are recruited and in what temporal pattern. Inhibitory interneurons provide both temporal and spatial tuning. The 'forward' flow from layer-4 excitatory neurons to layer 3 and from 3 to 5 activates predominantly pyramids. 'Back' projections, from 3 to 4 and 5 to 3, do not activate excitatory cells, but target interneurons. Despite, therefore, an increasing complexity in the information integrated as it is processed through these layers, there is little 'contamination' by 'back' projections. That layer 6 acts both as a primary input layer feeding excitation 'forward' to excitatory cells in other layers and as a higher-order layer with more integrated response properties feeding inhibition to layer 4 is discussed.

Selectivity in the inter-laminar connections made by neocortical neurones.

In this brief review of inter-laminar synaptic connections in neocortex a case is made for the hypothesis that axons select their targets, or neurones select their inputs with great specificity. A large part of the data discussed was obtained from dual intracellular recordings in slices of adult neocortex. The neurones innervated in a given layer by a given type of axon were not found to be a random selection of the cells in that layer. Rather in a layer to layer specific fashion, certain types of target cells are densely innervated while others are not contacted or receive only weak inputs. In another layer, the same axons may select other targets.