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Bureau, I.

Publications and source records attributed to Bureau, I..

6 recordsLinked to original sources

Clustered and diffuse sensory corticostriatal wirings define complementary interneuron circuits

In the striatum, interneurons tightly control the activity of output neurons, the striatal projection neurons (SPN). Among these striatal interneurons, parvalbumin-expressing (PV) and somatostatin-expressing (SOM) cells exhibit markedly distinct electrophysiological and anatomical properties, suggesting differential integration into striatal circuits and distinct forms of feedforward inhibition onto SPN. However, it remains unclear whether differences already emerge at the level of corticostriatal connectivity and if they shape specific interactions with cortical inputs to SPN. Here, we investigated the spatial organization of the projections from the primary and secondary somatosensory areas (S1 and S2), onto striatal PV and SOM interneurons and SPN. With a combination of anatomical tracing and functional circuit mapping, we characterized key features of corticostriatal connectivity, including input number, origin, spacing, overlap and strength. We found that input spacing and strength, at both the individual cell and population levels, were the principal features distinguishing PV and SOM interneurons. In contrast, connectivity differed primarily in input number and laminar organization across S1 and S2. Our findings suggest two potential modes of interaction between interneurons and SPN connectivity: one in which PV interneurons receive S1 inputs structured in large clusters, that densely overlap with those of neighboring SPN, providing an anatomical substrate for potential neuronal assemblies. And another in which SOM interneurons also receive abundant cortical inputs, but thinly disseminated across S1 and S2 and that overlap little with those of SPN, potentially shaping these cell integration through input cross-interaction. These cell-type principles of corticostriatal wiring may support distinct forms of striatal computation.

neuroscience↗

Lateralized foraging induces asymmetric corticostriatal plasticity in mice

With practice, animals perform reward-oriented actions faster and with less variability. The dorsal striatum (DS) plays a key role in this process, potentially through opposing changes in cortical input strength to the two main striatal projection neurons (D1- and D2-SPNs). To test this hypothesis, we trained mice in a foraging task requiring them to perform quarter-turns (QTs) in a single direction (counterclockwise, CCW) along the walls of square towers to collect drops of water. As training progressed, the number and speed of CCW QTs increased while the variability of their trajectory decreased. Whisker trimming in well-trained mice altered QTs kinematics, highlighting the role of tactile inputs in guiding these actions. Combining ex vivo patch-clamp recordings in the DS with glutamate uncaging in the barrel cortex, we mapped the cortical neurons monosynaptically connected to D1- or D2-SPNs and measured the strength of these connections in the contralateral hemispheres, relative to the turn direction. In well-trained mice, compared to naive controls, the contralateral hemisphere showed no major changes in D1- or D2-SPNs connectivity, despite increased excitation of cortical pyramidal neurons. In contrast, the ipsiversive hemisphere exhibited no change in cortical excitability but showed increased cortical connectivity and input strength to SPNs. These findings reveal an unexpected hemispheric asymmetry in corticostriatal connectivity during lateralized foraging, which may reflect a homeostatic process normalizing striatal activity across hemispheres despite unbalanced cortical input.

neuroscience↗

Sparse innervation and local heterogeneity in the vibrissal corticostriatal projection

The density and overlap of cortical axons in the dorsolateral striatum (DLS) have suggested that striatal neurons integrate widespread information from cortical regions that are functionally related. However, in vivo, DLS neuronal responses to sensory stimuli have shown unexpectedly high selectivity, raising questions about the actual degree of input convergence of functional corticostriatal projection on individual striatal cells. Here, we investigated this question by focusing on the projections from different whisker cortical columns, as they overlap in the striatum and are co-active during behavior. Using ex vivo patch-clamp recordings in the DLS and glutamate uncaging for focal stimulations in the barrel cortex, we were able to map the location of presynaptic neurons to individual striatal projection neurons (SPNs). We found that each SPN was innervated by cells located in a small number of whisker cortical columns scattered across the barrel field in the slice. Connectivity of single SPNs with cortical neurons was thus highly discontinuous horizontally, despite the presence of more potential connections. Moreover, connectivity patterns were specific to each cell, with neighboring SPNs sharing few common clusters of presynaptic cells in the cortex. Despite this sparse and distinct innervation of individual SPNs, the projection was topographically organized at the population level. Finally, we found similar innervation patterns for D1- and D2-type SPNs, but observed differences in synaptic strength in their connections with certain cortical layers, notably the associative layer 2/3. Our results suggest that the high convergence of somatosensory inputs to the striatum, enabled by diffuse and overlapping cortical innervation, is accomplished through sparse yet complementary connectivity to individual SPNs.

neuroscience↗

Somatostatin interneurons select dorsomedial striatal representations of the initial learning phase

The dorsomedial striatum (DMS) is an associative node involved in the adaptation of ongoing actions to the environmental context and in the initial formation of motor sequences. In early associative or motor learning phases, DMS activity shows a global decrease in neuron firing, eventually giving rise to a select group of active cells, whose number is correlated with animal performance. Unveiling how those representation emerge from DMS circuits is crucial for understanding plasticity mechanisms of early adjustments to learning a task. Here, we hypothesized that inhibitory microcircuits formed by local interneurons are responsible for the genesis of early DMS representation and associated task performance. Despite the low density of somatostatin (SOM)-positive cells, we observed that selective manipulation of SOM cells disrupted reorganization of DMS activity and modulated initial phases of learning in two behavioral contexts. This effect was cell-specific as manipulation of parvalbumin-positive interneurons had no significant effect. Finally, we identified the high plasticity of SOM innervation in the DMS as a key modulator of the SPN excitability and firing activity. Hence, SOM interneurons set the pace of early learning by actively controlling the remapping of DMS network activity.

neuroscience↗

Distinct subtypes of grey matter heterotopia show subtype-specific morpho-electric neuronal properties and dynamics of epileptiform activity in mice

Grey matter heterotopia (GMH) are neurodevelopmental disorders associated with abnormal cortical function and epilepsy. Subcortical band heterotopia (SBH) and periventricular nodular heterotopia (PVNH) are two well-recognized GMH subtypes in which neurons are misplaced, either forming nodules lining the ventricles in PVNH, or forming bands in the white matter in SBH. Although both PVNH and SBH are commonly associated with epilepsy, it is unclear whether these two GMH subtypes differ in terms of pathological consequences or, on the contrary, share common altered mechanisms. Here, we studied two robust preclinical models of SBH and PVNH, and performed a systematic comparative assessment of the physiological and morphological diversity of heterotopia neurons, as well as the dynamics of epileptiform activity and input connectivity. We uncovered a complex set of altered properties, including both common and distinct physiological and morphological features across heterotopia subtypes, and associated with specific dynamics of epileptiform activity. Taken together, these results suggest that pro-epileptic circuits in GMH are, at least in part, composed of neurons with distinct, subtype-specific, physiological and morphological properties depending on the heterotopia subtype. Our work supports the notion that GMH represent a complex set of disorders, associating both shared and diverging pathological consequences, and contributing to forming epileptogenic networks with specific properties. A deeper understanding of these properties may help to refine current GMH classification schemes by identifying morpho-electric signatures of GMH subtypes, to potentially inform new treatment strategies.

neuroscience↗

Lack of a key stage of hyper-connectivity between deep and superficial layers during barrel cortex development in a rat model of Absence Epilepsy

The development of cortical neuronal wiring is precisely orchestrated and goes through several stages, some of which coincide with critical periods when sensory experience is most influential. In particular, although ascending excitatory and inhibitory projections from the deep layer 5 to upper layers are first strong, they recede by the end of the critical period of their targets cells located in upper layers. Alterations in these transient innervations impair the construction of the later circuits that remain at adulthood, but it is unknown whether they could lead to pathologies. Here, we address this question in a genetic model of Absence Epilepsy, a neuro-developmental disease, where epileptogenesis occurs during the postnatal maturation of barrel cortex, the seizure initiation site. Using functional mapping by laser scanning photostimulation with glutamate uncaging in slices, we investigated the pattern of projections onto layers 2/3 pyramidal cells from 2-week old rats. We found that its maturation skipped the key stage during which pyramidal cells received strong projections from both excitatory and inhibitory neurons located in deep layers. At the same age, neuronal activity recorded in vivo with two-photon functional imaging was organized in fewer clusters than in control rat pups during this transient hyper-innervation. Later, around the onset of typical absence seizures ([~]1 month old), over-excitability of cells was observed across layers. Using this genetic model of childhood epilepsy, we provide first evidence that failure to develop this transient hyper-innervation from deep cortical layers plays a role in pathological neural dysfunctions. Significance StatementDuring development of cortex, innervation from deep to upper layers is thought to provide a temporary scaffold for the construction of the circuits that remain at adulthood. Whether an alteration in this sequence causes brain malfunctions in neuro-developmental diseases is unknown. Using functional approaches, we investigated in a genetic model of Absence Epilepsy and control rats the maturation of innervation onto layer 2/3 pyramidal cells of barrel cortex and the cell organization into neuronal assemblies. We found that development in this model lacks this early surge of connectivity with deep layers and the concomitant structuring into multiple assemblies. Later on, at seizure onset, neurons in all layers are hyper-excitable, suggesting this feature of epilepsy develops from prior connectivity defects.

neuroscience↗