Biology subjects

Druart, M.

Publications and source records attributed to Druart, M..

5 recordsLinked to original sources

bioRxiv2026

The Cellular and Synaptic Actions of Dopamine During Behavior

Dopamine signaling in the striatum is essential for a wide range of functions, from reward learning to motor vigor and behavioral flexibility. Although dopamine signals fluctuate on sub-second timescales, how these signals are translated into lasting changes in striatal circuit function remains unknown. Resolving this requires cell-type-specific measurements of synaptic and intrinsic properties during behavior, a longstanding technical challenge. Here, we combined in vivo whole-cell membrane potential recordings, simultaneous monitoring and bidirectional manipulation of dopamine signaling in awake, behaving mice to examine how dopamine shapes corticostriatal circuits. Acute manipulations of dopamine over seconds to minutes produced only modest effects on corticostriatal synaptic transmission and no detectable changes in membrane potential dynamics or intrinsic excitability. By contrast, associative learning robustly strengthened identified corticostriatal synapses onto both D1- and D2-expressing spiny projection neurons, yet only D1-SPN plasticity required dopamine signaling. These findings challenge models in which dopamine acts rapidly to tune striatal excitability and identify learning related plasticity as its principal mechanism for shaping striatal circuits in vivo.

neuroscience↗

bioRxiv2026

LSD persistently disrupts affective pain processing

Psychedelics produce long-lasting effects, but their circuit mechanisms remain unclear. Here we show that, in rats, a single dose of lysergic acid diethylamide (LSD) persistently reduces pain affect. This effect is recapitulated by local administration in the anterior cingulate cortex (ACC), but not primary somatosensory cortex. Neuropixels recordings reveal that LSD suppresses stimulus-evoked nociceptive responses in the ACC, reducing the encoding of aversive value. Despite increasing intrinsic excitability ex vivo, LSD reduces the maximum stimulus-evoked firing of ACC neurons in vivo, indicating a dissociation between excitability and sensory encoding. Together, these findings show that psychedelics disrupt the cortical transformation of nociceptive input into aversive representations.

neuroscience↗

bioRxiv2024

Cell-type specific auditory responses in the striatum are shaped by feed forward inhibition

Summary/AbstractThe posterior "tail" region of the striatum receives dense innervation from sensory brain regions and has been demonstrated to play a role in behaviors that require sensorimotor integration including discrimination1,2, avoidance3 and defense4 responses. The output neurons of the striatum, the D1 and D2 striatal projection neurons (SPNs) that make up the direct and indirect pathways, respectively, are thought to play differential roles in these behavioral responses, although it remains unclear if or how these neurons display differential responsivity to sensory stimuli. Here, we used whole-cell recordings in vivo and ex vivo to examine the strength of excitatory and inhibitory synaptic inputs onto D1 and D2 SPNs following the stimulation of upstream auditory pathways. While D1 and D2 SPNs both displayed stimulus-evoked depolarizations, D1 SPN responses were stronger and faster for all stimuli tested in vivo as well as in brain slices. This difference did not arise from differences in the strength of excitatory inputs but from differences in the strength of feed forward inhibition. Indeed, fast spiking interneurons, which are readily engaged by auditory afferents exerted stronger inhibition onto D2 SPNs compared to D1 SPNs. Our results support a model in which differences in feed forward inhibition enable the preferential recruitment of the direct pathway in response to auditory stimuli, positioning this pathway to initiate sound-driven actions.

neuroscience↗

bioRxiv2022

Serotonin sensing by microglia conditions the proper development of neuronal circuits and of social and adaptive skills

The proper maturation of emotional and sensory circuits requires a fine tuning of serotonin (5-HT) level during early postnatal development. Consistently, dysfunctions of the serotonergic system have been associated with neurodevelopmental psychiatric diseases, including autism spectrum disorders (ASD). However, the mechanisms underlying the developmental effects of 5-HT remain partially unknown, one obstacle being the action of 5-HT on different cell types. Here, we focused on microglia, which play a role in brain wiring refinement, and we investigated whether the control of these cells by 5-HT is relevant for neurodevelopment and spontaneous behaviors. Since the main 5-HT sensor in microglia is the 5-HT2B receptor subtype, we prevented 5-HT signaling specifically in microglia by conditionally invalidating Htr2b gene in these cells. We observed that abrogating the serotonergic control of microglia neonatally impacts the phagolysosomal compartment of these cells and their proximity to synapses, and perturbs neuronal circuits maturation. Furthermore, this early ablation of microglial 5-HT2B receptors leads to adult hyperactivity in a novel environment and behavioral defects in sociability and flexibility. Importantly, we show that these behavioral alterations result from a developmental effect, since they are not observed when microglial Htr2b invalidation is induced later, at P30 onward. Thus, a primary alteration of 5-HT sensing in microglia, during a critical time window between birth and P30, is sufficient to impair social and flexibility skills. This link between 5-HT and microglia may explain the association between serotonergic dysfunctions and behavioral traits, like impaired sociability and inadaptability to novelty, which are prominent in several psychiatric disorders such as ASD.

neuroscience↗

bioRxiv2020

Elevated expression of complement C4 in the mouse prefrontal cortex causes schizophrenia-associated phenotypes

Accumulating evidence supports immune involvement in the pathogenesis of schizophrenia, a severe psychiatric disorder. In particular, high expression variants of C4, a gene of the innate immune complement system, were shown to confer susceptibility to schizophrenia. However, how elevated C4 expression may impact brain circuits remains largely unknown. We used in utero electroporation to overexpress C4 in the mouse prefrontal cortex (PFC). We found reduced glutamatergic input to pyramidal cells of juvenile and adult, but not of newborn C4-overexpressing (C4-OE) mice, together with decreased spine density, which mirrors spine loss observed in the schizophrenic cortex. Using time-lapse two-photon imaging in vivo, we observed that these deficits were associated with decreased dendritic spine gain and elimination in juvenile C4-OE mice, which may reflect poor formation and/or stabilization of immature spines. In juvenile and adult C4-OE mice we found evidence for NMDA receptor hypofunction, another schizophrenia-associated phenotype, and synaptic accumulation of calcium-permeable AMPA receptors. Alterations in cortical GABAergic networks have been repeatedly associated with schizophrenia. We found that functional GABAergic transmission was reduced in C4-OE mice, in line with diminished GABA release probability from parvalbumin interneurons, lower GAD67 expression and decreased intrinsic excitability in parvalbumin interneurons. These cellular abnormalities were associated with working memory impairment. Our results substantiate the causal relationship between an immunogenetic risk factor and several distinct cortical endophenotypes of schizophrenia, and shed light on the underlying cellular mechanisms.

neuroscience↗