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 D01 Functional roles of inhibition in the somatosensory system of rodents

Parallel sensory processing is thought to allow biased selection of specific stimulus features based on external conditions, behavioral contexts, and prior experience. Importantly, although ascending pathways are thought to target different cortical layers, some intermixing may exist within layers. We hypothesize that the classical laminar cortical organization should be tested against pathway-specific connections. Our preliminary data indicates that in the somatosensory system the pathway specificity of neurons can be identified electrophysiologically using a repetitive whisker stimulation paradigm. The differential laminar distribution of receptors for various neuromodulators in primary sensory cortical areas strongly suggests that shifts in brain-states, such as between drowsy and awake states or due to increased attention, change the activity profile across different layers and cell types. While previous in-vitro and in vivo studies demonstrated that neuromodulators and shifts in brain-states alter the laminar activity profile, their results are far from being consistent, in particular regarding excitatory and inhibitory effects. Our main goal is to study the effects of brain states and neuromodulators on the balance between excitation and inhibition (E/I balance) during ongoing and sensory evoked activities and across different types of cells and layers. We will modify the state of mice’s brain using three complimentary methods while recording the ongoing and whisker-evoked excitatory and inhibitory synaptic potentials of individual cells in the barrel cortex. In one, we will use local application of specific agonists of acetylcholine, noradrenaline or corticotropin-releasing factor or use local optogentic activation of their endogenous systems. In another approach, we will alter the state of the animal’s brain by modifying the depth of anesthesia, and finally we will use behavioral cues to change the level of arousal and attention of awake restrained animals.  These results will ultimately elucidate the mechanisms that regulate E/I balance across different cell types and behavioral conditions.    

 

Figure 1. Studying the effect of brain states on E/I balance. A. Schematic illustration of the adaptation pattern in the brainstem trigeminal complex. Increasing the intensity of vibrissa stimulation entailed more adaption in paralemniscal neurons, whereas it caused less adaptation in lemniscal cells. B. The approach for testing the effect of brain states on E/I balance. Steps of current were injected into the cell throughout the recording session while the depth of anesthesia was modified. C. The optopatcher will be used to allow simultaneous whole cell recording and light stimulation using a single device. D.  Expression of ChR2 in the basal forebrain of CHAT mice. The firing of a single cell in the basal forebrain recorded and stimulated using the optopatcher.