Inter- and Intra-laminar Connections of Pyramidal Cells in Neocortex.

A. Peter Bannister and Alex M. Thomson

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Department of Pharmacology, School of Pharmacy, 29-39 Brunswick Square,

London. WC1N 1AX, United Kingdom.

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The flow of excitation through cortical columns has long since been predicted by studying the axonal projection patterns of excitatory pyramidal neurones situated within different laminae. In grossly simplified terms and assuming random connectivity, such studies predict that input from the thalamus terminates primarily in layer 4, is relayed 'forward' to layer 3, then to layers 5 and 6 from where the modified signal may exit the cortex. Projection patterns also indicate 'back' projections from layer 5 to 3 and layer 6 to 4. More recently it has become clear that the interconnections between these layers are not random; forward projections primarily contact other pyramidal neurones and back projections innervate inhibitory interneurones. This indicates that presynaptic axons or the postsynaptic dendrites are capable of selecting their synaptic partners and that this selectivity is layer dependent.

We have studied pyramidal cell targeting in circuits both within and between the layers using paired intracellular recordings with biocytin filling and have begun to identify further levels of selectivity through the preferential targeting of electrophysiological and/or morphologically distinct pyramidal subtypes.

For example, at connections between pyramidal neurones in layer 4, both pre- and post-synaptic neurones always exhibited regular spiking (RS) or phasic (RS-2) discharge characteristics and never involved high frequency, rapidly adapting (burst firing-like) cells that comprise ~37% of layer 4 cells recorded. All putative synapses were made with the basal dendrites of target pyramidal neurones. Connections between layers 4 and 3 included all subtypes. These data suggest the selective innervation of electrophysiological subtypes of pyramidal cells in layer 4 to layer 4 connections as well as preferential innervation of basal dendritic compartments.

The descending axons of layer 3 pyramids do not ramify extensively in layer 4 and very rarely innervate the layer 4 spiny cells. They do however arborise in layer 5 and make frequent selective synapses with large intrinsically burst firing pyramidal cells that have well developed apical dendritic tufts. Connections with this subtype were observed at a rate of 1 in every 2 tests when the presynaptic cell was within ~50?m of the ascending postsynaptic apical dendrite. In contrast, the smaller, RS pyramids whose basal dendrites occupy the same volume of tissue in layer 5 but whose apical dendrites did not reach the superficial layers did not receive input from layer 3.

While a number of questions remain, including from where and which neurones the RS layer 5 pyramids and the apical dendrites of layer 4 pyramids receive input, these data suggest that while the locations of axonal profiles remain relevant indices for the distribution of excitation from layer to layer, further levels of selectivity and parallel streams of cortical processing within the columns may utilise different pyramidal subclasses.

(Supported by Novartis Pharma and the Medical Research Council)

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