Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex

Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory barrel cortex of awake behaving mice. SOM neurons were spontaneously active during periods of quiet wakefulness. However, SOM neurons hyperpolarized and reduced action potential firing in response to both passive and active whisker sensing, in contrast with all other recorded types of nearby neurons, which were excited by sensory input. Optogenetic inhibition of SOM neurons increased burst firing in nearby excitatory neurons. We hypothesize that the spontaneous activity of SOM neurons during quiet wakefulness provides a tonic inhibition to the distal dendrites of excitatory pyramidal neurons. Conversely, the inhibition of SOM cells during active cortical processing likely enhances distal dendritic excitability, which may be important for top-down computations and sensorimotor integration.

Microcircuits of excitatory and inhibitory neurons in layer 2/3 of mouse barrel cortex

Michael Avermann, Wulfram Gerstner, Céline Matéo, Carl Petersen, Christian Tomm

Avermann M, Tomm C, Mateo C, Gerstner W, Petersen CC. Microcircuits of excitatory and inhibitory neurons in layer 2/3 of mouse barrel cortex. J Neurophysiol 107: 3116-3134, 2012. First published March 7, 2012; doi:10.1152/jn.00917.2011.-Synaptic interactions between nearby excitatory and inhibitory neurons in the neocortex are thought to play fundamental roles in sensory processing. Here, we have combined optogenetic stimulation, whole cell recordings, and computational modeling to define key functional microcircuits within layer 2/3 of mouse primary somatosensory barrel cortex. In vitro optogenetic stimulation of excitatory layer 2/3 neurons expressing channelrhodopsin-2 evoked a rapid sequence of excitation followed by inhibition. Fast-spiking (FS) GABAergic neurons received large-amplitude, fast-rising depolarizing postsynaptic potentials, often driving action potentials. In contrast, the same optogenetic stimulus evoked small-amplitude, subthreshold postsynaptic potentials in excitatory and non-fast-spiking (NFS) GABAergic neurons. To understand the synaptic mechanisms underlying this network activity, we investigated unitary synaptic connectivity through multiple simultaneous whole cell recordings. FS GABAergic neurons received unitary excitatory postsynaptic potentials with higher probability, larger amplitudes, and faster kinetics compared with NFS GABAergic neurons and other excitatory neurons. Both FS and NFS GABAergic neurons evoked robust inhibition on postsynaptic layer 2/3 neurons. A simple computational model based on the experimentally determined electrophysiological properties of the different classes of layer 2/3 neurons and their unitary synaptic connectivity accounted for key aspects of the network activity evoked by optogenetic stimulation, including the strong recruitment of FS GABAergic neurons acting to suppress firing of excitatory neurons. We conclude that FS GABAergic neurons play an important role in neocortical microcircuit function through their strong local synaptic connectivity, which might contribute to driving sparse coding in excitatory layer 2/3 neurons of mouse barrel cortex in vivo.

American Physiological Society2012

Optogenetic Probing of Cortical Synaptic Circuits Measured Through in Vivo Whole-Cell Recordings in the Mouse Barrel Cortex

Céline Matéo

Although neocortex underlies higher-order brain functions, little is known about the synaptic interactions that drive neocortical microcircuit function in vivo. The neocortex is spontaneously active in vivo so I explored how such spontaneous network activity affects in vivo the interactions between excitatory and inhibitory neurons in the barrel cortex. To this aim, I have focused on the layer 2/3 microcircuit of the C2 barrel column driving sensory processing for the C2 whisker, and combined in vivo whole-cell patch-clamp recordings in anesthetised and awake head-restrained mice with optogenetic stimulation, that allows controlling the activity of genetically defined neurons with light. I expressed channelrhodopsin-2 (ChR2), a light-gated cation channel to evoke action potentials in excitatory neurons with brief light pulses. The impact of this optogenetic stimulus was measured on the membrane potential dynamics of their postsynaptic target neurons. The optogenetic stimulus drove reliable action potentials in ChR2-expressing excitatory neurons, independent of the state of ongoing spontaneous cortical activity. In contrast, I found a marked modulation of light-evoked postsynaptic responses in ChR2-non-expressing excitatory neurons by cortical activity. During spontaneously hyperpolarised periods (DOWN state), optogenetic stimulation resulted in depolarisations of postsynaptic excitatory neurons, while during depolarised periods (UP state), the response was significantly smaller and shorter. The optogenetic stimulus drove the membrane potential of postsynaptic excitatory layer 2/3 neurons towards reversal potentials, which were hyperpolarised relative to action potential threshold, leading to a reduction in firing rates. Targeting whole-cell recordings to GFP-labelled GABAergic layer 2/3 neurons with two-photon microscopy revealed that both fast-spiking and non-fast-spiking inhibitory postsynaptic neurons were rapidly driven to fire action potentials, preferentially from UP states. Such rapid activation of inhibitory neurons in the UP state is likely to be responsible for decreasing firing rate in excitatory neurons. As a result, optogenetic stimulation of a given set of excitatory neurons results in a state-dependent recruitment of inhibitory neurons that limit the spread of excitation within the layer 2/3 microcircuit. The data presented here indicates that a powerful inhibitory loop within the cortical microcircuit rapidly balances excitation with inhibition and enforces sparse coding of layer 2/3 excitatory neurons.

EPFL2011

Cell-type-specific nicotinic input disinhibits mouse barrel cortex during active sensing

Sylvain Crochet, Célia Roxane Gasselin, Benoît Hohl, Carl Petersen

Fast synaptic transmission relies upon the activation of ionotropic receptors by neurotransmitter release to evoke postsynaptic potentials. Glutamate and GABA play dominant roles in driving highly dynamic activity in synaptically connected neuronal circuits, but ionotropic receptors for other neurotransmitters are also expressed in the neocortex, including nicotinic receptors, which are non-selective cation channels gated by acetylcholine. To study the function of non-glutamatergic excitation in neocortex, we used two-photon microscopy to target whole-cell membrane potential recordings to different types of genetically defined neurons in layer 2/3 of primary somatosensory barrel cortex in awake head-restrained mice combined with pharmacological and optogenetic manipulations. Here, we report a prominent nicotinic input, which selectively depolarizes a subtype of GABAergic neuron expressing vasoactive intestinal peptide leading to disinhibition during active sensorimotor processing. Nicotinic disinhibition of somatosensory cortex during active sensing might contribute importantly to integration of top-down and motor-related signals necessary for tactile perception and learning.