Biology subjects

Richevaux, L.

Publications and source records attributed to Richevaux, L..

4 recordsLinked to original sources

bioRxiv2026

Circuit organization of the forelimb-related M2-to-M1 corticocortical pathway in the mouse

Communication from secondary (M2, premotor) to primary (M1) motor cortex is implicated in forelimb motor control. We investigated the underlying synaptic circuits in this corticocortical pathway in male and female mice using cell-type-specific optogenetic-electrophysiology methods, focusing on identifying the cell-type-specific synaptic connections in the excitatory and feedforward inhibitory circuits impinging on cervically projecting M1 corticospinal neurons. In forelimb M1 brain slices, recordings from layer 5B corticospinal neurons during brief photostimulation of M2 axons showed strong monosynaptic excitatory currents that, although accompanied by potent feedforward inhibitory currents, were capable of evoking action potentials (APs) in most neurons. In contrast, responses in layer 2/3 pyramidal neurons were generally much weaker. Parvalbumin-expressing neurons (PV), particularly in deeper layers, showed direct excitation from M2 axons without feedforward inhibition, and could fire APs robustly. Somatostatin (SST) neurons received generally weak inputs, whereas VIP and Ndnf neurons received stronger excitation and inhibition from M2 axons. Corticospinal neurons received little or no local inhibition from Ndnf and VIP interneurons, but relatively strong soma-targeting PV and dendrite-targeting SST inhibitory inputs, as functionally imaged by laser-scanning synaptic input mapping ("sCRACM"). The domains of PV and SST inputs were partly overlapping around the corticospinal somata, but broader for PV and more vertical for SST inputs. Collectively, the results provide a working model for the cell-type-specific synaptic circuits of this "top-down" corticocortical pathway, organized around direct M2 excitation and PV-mediated inhibition of M1 corticospinal neurons. SIGNIFICANCE STATEMENTCervically projecting corticospinal neurons in the primary motor cortex (M1) serve as the most direct conduits by which motor cortical activity reaches and influences spinal circuits controlling forelimb movements. Corticospinal activity is in turn influenced by inputs from multiple upstream areas. Here we studied the inputs from the secondary motor cortex (M2), a premotor-like area in the mouse, and characterized the patterns of synaptic connectivity formed by M2 axons onto multiple postsynaptic cell types in M1. The resulting "wiring diagram" suggests that these inter-areal circuits are configured to give premotor cortex privileged access to modulate M1 corticospinal output, through cell-type-specific connections and inhibitory mechanisms.

neuroscience↗

bioRxiv2023

Integration of thalamic and retrosplenial inputs in presubicular layer 3 gates cross-laminar bursting signal to upstream head direction circuit

Head-direction (HD) signals function as the brains internal compass. They are organized as an attractor, and anchor to the environment via visual landmarks. Here we examine how thalamic HD signals and visual information from the retrosplenial cortex combine in the presubiculum. We find that monosynaptic excitatory connections from anterior thalamic nucleus and from retrosplenial cortex converge on single layer 3 pyramidal neurons in the dorsal portion of mouse presubiculum. Independent dual wavelength photostimulation of these inputs in slices leads to action potential generation preferentially for near-coincident inputs, indicating that layer 3 neurons can transmit a visually matched HD signal to medial entorhinal cortex. Layer 4 neurons, which innervate the lateral mammillary nucleus, form a second step in the association of HD and landmark signals. They receive little direct input from thalamic and retrosplenial axons. We show that layer 4 cells are excited di-synaptically, transforming regular spiking activity into bursts of action potentials, and that their firing is enhanced by cholinergic agonists. Thus, a coherent sense of orientation involves projection specific translaminar processing in the presubiculum, where neuromodulation facilitates landmark updating of HD signals in the lateral mammillary nucleus.

neuroscience↗

bioRxiv2020

Oligodendrocyte secreted factors shape hippocampal GABAergic neuron transcriptome and physiology

Oligodendrocytes form myelin for central nervous system axons and release factors which signal to neurons during myelination. Here, we ask how oligodendroglial factors influence hippocampal GABAergic neuron physiology. In mixed hippocampal cultures GABAergic neurons fired action potentials of short duration and received high frequencies of excitatory synaptic events. In purified neuronal cultures without glial cells, GABAergic neuron excitability increased and the frequency of synaptic events decreased. These effects were largely reversed by adding oligodendrocyte conditioned medium. We compared the transcriptomic signature with the electrophysiological phenotype of single neurons in these three culture conditions. Genes expressed by single pyramidal or GABAergic neurons largely conformed to expected cell-type specific patterns. Multiple genes of GABAergic neurons were significantly downregulated by the transition from mixed cultures containing glial cells to purified neuronal cultures. Levels of these genes were restored by the addition of oligodendrocyte conditioned medium to purified cultures. Clustering genes with similar changes in expression between different culture conditions revealed processes affected by oligodendroglial factors. Enriched genes are linked to roles in synapse assembly, action potential generation and transmembrane ion transport, including of zinc. These results provide new insight into the molecular targets by which oligodendrocytes influence neuron excitability and synaptic function.

neuroscience↗

bioRxiv2018

Optogenetic stimulation of long-range inputs and functional characterization of connectivity in patch-clamp recordings in mouse brain slices

Knowledge of cell type specific synaptic connectivity is a crucial prerequisite for understanding brain wide neuronal circuits. The functional investigation of long-range connections requires targeted recordings of single neurons combined with the specific stimulation of identified distant inputs. This is often difficult to achieve with conventional, electrical stimulation techniques, because axons from converging upstream brain areas may intermingle in the target region. The stereotaxic targeting of a specific brain region for virus-mediated expression of light sensitive ion channels allows to selectively stimulate axons coming from that region with light. Intracerebral stereotaxic injections can be used in well-delimited structures, such as the anterodorsal thalamic nuclei, and also in other subcortical or cortical areas throughout the brain.\n\nHere we describe a set of techniques for precise stereotaxic injection of viral vectors expressing channelrhodopsin in the anterodorsal thalamus, followed by photostimulation of their axon terminals in hippocampal slices. In combination with whole-cell patch clamp recording from a postsynaptically connected presubicular neuron, photostimulation of thalamic axons allows the detection of functional synaptic connections, their pharmacological characterization, and the evaluation of their strength in the brain slice preparation. We demonstrate that axons originating in the anterodorsal thalamus ramify densely in presubicular layers 1 and 3. The photostimulation of Chronos expressing thalamic axon terminals in presubiculum initiates short latency postsynaptic responses in a presubicular layer3 neuron, indicating a monosynaptic connection. In addition, biocytin filling of the recorded neuron and posthoc revelation confirms the layer localization and pyramidal morphology of the postsynaptic neuron. Taken together, the optogenetic stimulation of long-range inputs in ex vivo brain slices is a useful method to determine the cell-type specific functional connectivity from distant brain regions.

neuroscience↗