Layer 6 Cortico-thalamic Pyramidal Cells Preferentially Innervate Interneurons and Generate Facilitating EPSPs

Abstract

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.

Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors

“…The mean membrane properties of layer VI pyramidal neurons recorded (n ϭ 325) were 92 Ϯ 1 mV spike amplitude, 240 Ϯ 11 M⍀ input resistance, and Ϫ78 Ϯ 1 mV resting potential. Because corticothalamic neurons are suggested to send a collateral axon to local circuit interneurons (West et al, 2006), we also collected data from layer VI fast-spiking interneurons. These cells were patched based on their small, circular morphology and were confirmed electrophysiologically by their characteristic, fast spiking pattern on injection of depolarizing current pulses.…”

“…Our preliminary analysis suggested that the firing properties of the layer VI pyramidal neurons in rat could be a useful criterion to predict which neurons were likely to have nicotinic currents, as shown in Figure 2. Recent work has suggested that corticothalamic layer VI neurons are regular spiking neurons (West et al, 2006), whereas layer VI corticocortical neurons tend to be burst-spiking neurons (Mercer et al, 2005). Therefore, we compared nicotinic inward currents between regular spiking and bursting neurons from rats from ages P15 to P42.…”

“…Because recent work suggests that corticothalamic neurons send a local collateral axon to fast-spiking interneurons in cortical layer VI (West et al, 2006), we recorded from a sample of these neurons (age range examined, P15-P39). We found that in 13 of 14 fast-spiking interneurons in layer VI, acetylcholine in the presence of atropine significantly increased the frequency of sEPSCs (Kolmogorov-Smirnov test; p Ͻ 0.01), as illustrated in Figure 7.…”

Robust but delayed thalamocortical activation of dendritic-targeting inhibitory interneurons

“…Infragranular pyramidal cells, including putative CTNs, make facilitating synaptic connections on nearby interneurons (32,33). To rule out that antidromically activated CTN axon collaterals contributed to the facilitating EPSPs in layer 5 SOMϩ interneurons, we recorded from infragranular, ''regular-spiking'' (Fig.…”

Depressing synapse as a detector of frequency change

“…There are at least three common inter-spike intervaldependent measures of the short-term synaptic depression: Paired Pulse Ratio (PPR) as in (Gompf and Allen, 2004), Paired Pulse Depression (PPD) as in (Bannister and Thomson, 2007) and II-PSP-Integral to I-PSP-Integral ratio as in (Thomson, 1997). One can also mention consecutive postsynaptic responses to dual presynaptic stimulation, e.g (Baldelli et al, 2007) (PSC) and (West et al, 2006)(PSP), or steady state PSC amplitude (Sun et al, 2005) .…”