Parvalbumin-Expressing GABAergic Neurons in Mouse Barrel Cortex Contribute to Gating a Goal-Directed Sensorimotor Transformation

Sensory processing in neocortex is primarily driven by glutamatergic excitation, which is counterbalanced by GABAergic inhibition, mediated by a diversity of largely local inhibitory interneurons. Here, we trained mice to lick a reward spout in response to whisker deflection, and we recorded from genetically defined GABAergic inhibitory neurons in layer 2/3 of the primary somatosensory barrel cortex. Parvalbumin-expressing (PV), vasoactive intestinal peptide-expressing (VIP), and somatostatin-expressing (SST) neurons displayed distinct action potential firing dynamics during task performance. Whereas SST neurons fired at low rates, both PV and VIP neurons fired at high rates both spontaneously and in response to whisker stimulation. After an initial outcome-invariant early sensory response, PV neurons had lower firing rates in hit trials compared to miss trials. Optogenetic inhibition of PV neurons during this time period enhanced behavioral performance. Hence, PV neuron activity might contribute causally to gating the sensorimotor transformation of a whisker sensory stimulus into licking motor output.

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

Yves Kremer, Carl Petersen

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.

Nature Publishing Group2012

The excitatory neuronal microcircuit of the C2 column in the mouse primary somatosensory cortex

Sandrine Lefort

Rodents are nocturnal animals gathering information about their surroundings by using highly sensitive detectors laid out on their snout. Like humans use their fingertips to apprehend textures, rodents use their whiskers to build a spatial representation of their environment, locate objects and discriminate fine textures. The most remarkable feature of the somatosensory whisker system consists in the isomorphic correspondence of each whisker with discrete cytoarchitectonic units in layer 4 of the primary somatosensory "barrel" cortex. These layer 4 barrels are the first step towards the integration of the sensory information within the neocortex and form the core of each cortical barrel column. To further our understanding of sensory processing, it becomes evident that studying the synaptic wiring of a specific barrel column will provide useful information. In this thesis work, we specifically investigate the excitatory wiring diagram of the C2 barrel related column. The functional location of our preferred column was mapped in vivo using intrinsic optical imaging upon C2 whisker deflection. The excitatory microcircuit of the C2 barrel column was investigated in vitro using simultaneous multiple whole-cell patch clamp recordings in the current clamp mode. We show that layer 4, through its highly recurrent and strong network, acts as the main excitatory driving force, spreading information across the entire cortical column. We demonstrate that supragranular layers are involved both in intralaminar recurrent circuits and top-down relations with postsynaptic partners in specific subjacent layers. The last relay of the excitation flow consists of the infragranular layers that integrate input from the whole column, and form the output of the cortical computation. Finally, by assessing the diversity of short-term dynamics of a subset of excitatory connections, we point out the complexity of sensory processing and the long journey remaining to unravel the synaptic mechanisms underlying sensory perception.

EPFL2008

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.