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Shankar Sachidhanadam"Membrane potential correlates of sensory perception"

Abstract :

In order to understand how sensory information can be used to guide goal-directed behaviors, we trained mice in a whisker stimulus detection task. Over a few days of training sessions, head-restrained and water-restricted mice learned that they could obtain a water reward by licking a spout immediately after a single brief C2 whisker deflection. Pharmacological inactivation of the corresponding C2 barrel column of well-trained mice markedly reduced behavioral performance. Optogenetic stimulation of excitatory neurons in the C2 barrel column was able to substitute for whisker stimulation in both learning and execution of the detection task. The barrel cortex therefore plays a critical role in the sensorimotor transformation of a detected whisker stimulus into a goal-directed licking motor output. Whole-cell recordings were targeted to layer 2/3 of the C2 barrel column to study the correlation between membrane potential and behavior. Across the population of recorded neurons, the sensory-evoked membrane potential response consisted of a complex, biphasic subthreshold depolarisation with sparse action potential firing. The early sensory-evoked response reliably represented the whisker stimulus across trials by driving membrane potential towards cell-specific reversal potentials. The early sensory response was not different comparing hit and miss trials, but it was larger in naive animals. A late depolarisation, with an elevated spike rate, preceded the lick response on hit trials, but was reduced on miss trials. The late depolarisation thus correlated with perceptual report and it might result from long-range excitatory input from reciprocally connected areas, such as motor cortex. The late depolarisation evoked by whisker stimulation in trained mice was replaced by a hyperpolarised response in naive mice. The detection task was compatible with a wide range of brain states, including cortical states characterised by slow, large-amplitude, synchronous membrane potential fluctuations. However, trained mice on average had more desynchronised cortical states than naive mice. Our data begin to provide a detailed description of the neural events in layer 2/3 mouse barrel cortex contributing to a simple form of sensory perception.

Selected publications

Kainate receptors act as conditional amplifiers of spike transmission at hippocampal mossy fiber synapses.
Sachidhanandam S, Blanchet C, Jeantet Y, Cho YH, Mulle C. J Neurosci. 2009 Apr 15;29(15):5000-8.
GluR6/KA2 kainate receptors mediate slow-deactivating currents. Barberis A, Sachidhanandam S, Mulle C. J Neurosci. 2008 Jun 18;28(25):6402-6.
Short-term plasticity of kainate receptor-mediated EPSCs induced by NMDA receptors at hippocampal mossy fiber synapses. Rebola N, Sachidhanandam S, Perrais D, Cunha RA, Mulle C. J Neurosci. 2007 Apr 11;27(15):3987-93.
Distinct subunits in heteromeric kainate receptors mediate ionotropic and metabotropic function at hippocampal mossy fiber synapses. Ruiz A, Sachidhanandam S, Utvik JK, Coussen F, Mulle C.
J Neurosci. 2005 Dec 14;25(50):11710-8.

Scientific focus :

After obtaining my PhD at the University of Bordeaux 2, I joined the laboratory of Prof. Carl Petersen at the EPFL, in Lausanne, as a postdoctoral fellow. I am focusing on the role of sensory processing in goal directed behavior, using the mouse whisker system as a model. I use the 2 photon targeted whole cell patch clamp recording technique to record from neurons in the whisker somatosensory cortex, in awake behaving mice.

Christophe Mulle (mulle @