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The dynamic I-V curve method was recently introduced for the efficient experimental generation of reduced neuron models. The method extracts the response properties of a neuron while it is subject to a naturalistic stimulus that mimics in vivo-like fluctuating synaptic drive. The resulting history-dependent, transmembrane current is then projected onto a one-dimensional current-voltage relation that provides the basis for a tractable non-linear integrate-and-fire model. An attractive feature of the method is that it can be used in spike-triggered mode to quantify the distinct patterns of post-spike refractoriness seen in different classes of cortical neuron. The method is first illustrated using a conductance-based model and is then applied experimentally to generate reduced models of cortical layer-5 pyramidal cells and interneurons, in injected-current and injected- conductance protocols. The resulting low-dimensional neuron models—of the refractory exponential integrate-and-fire type—provide highly accurate predictions for spike-times. The method therefore provides a useful tool for the construction of tractable models and rapid experimental classification of cortical neurons

Feeding satisfies metabolic need but is also controlled by external stimuli like palatability or predator threat. Nucleus accumbens shell (NAcSh) projections to the lateral hypothalamus (LH) are implicated in mediating such feeding control but the neurons involved and their mechanism of action remain elusive. We show that dopamine D1R expressing NAcSh neurons (D1R MSNs) provide the dominant source of accumbal inhibition to LH and provide rapid control over feeding via LH GABA neurons. In freely feeding mice D1R MSN activity reduced during consumption while their optogenetic inhibition prolonged feeding even in the face of distracting stimuli. Conversely activation of D1R MSN terminals in LH was sufficient to abruptly stop ongoing consumption even during hunger. Direct inhibition of LH GABA neurons which received input from D1R MSNs fully recapitulated these findings. Together our study resolves a feeding circuit that overrides immediate metabolic need to allow rapid consumption control in response to changing external stimuli.

The dynamic I–V curve method was recently introduced for the efficient experimental generation of reduced neuron models. The method extracts the response properties of a neuron while it is subject to a naturalistic stimulus that mimics in vivo-like fluctuating synaptic drive. The resulting history-dependent, transmembrane current is then projected onto a one-dimensional current–voltage relation that provides the basis for a tractable non-linear integrate-and-fire model. An attractive feature of the method is that it can be used in spike-triggered mode to quantify the distinct patterns of post-spike refractoriness seen in different classes of cortical neuron. The method is first illustrated using a conductance-based model and is then applied experimentally to generate reduced models of cortical layer-5 pyramidal cells and interneurons, in injected-current and injected- conductance protocols. The resulting low-dimensional neuron models—of the refractory exponential integrate-and-fire type—provide highly accurate predictions for spike-times. The method therefore provides a useful tool for the construction of tractable models and rapid experimental classification of cortical neurons.

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.

Neurons process information through spatiotemporal integration of synaptic input. Synaptic transmission between any given pair of neurons is typically a dynamic process with presynaptic action potentials (APs) evoking depressing or facilitating postsynaptic potentials when presynaptic APs occur within hundreds of milliseconds of each other. In order to understand neocortical function, it is therefore important to investigate such short-term synaptic plasticity at synapses between different types of neocortical neurons. Here, we examine short-term synaptic dynamics between excitatory neurons in different layers of the mouse C2 barrel column through in vitro whole-cell recordings. We find layer-dependent short-term plasticity, with depression being dominant at many synaptic connections. Interestingly, however, presynaptic layer 2 neurons predominantly give rise to facilitating excitatory synaptic output at short interspike intervals of 10 and 30 ms. Previous studies have found prominent burst firing of excitatory neurons in supragranular layers of awake mice. The facilitation we observed in the synaptic output of layer 2 may, therefore, be functionally relevant, possibly serving to enhance the postsynaptic impact of burst firing.