Biology subjects

Baude, A.

Publications and source records attributed to Baude, A..

7 recordsLinked to original sources

bioRxiv2025

GABAergic neurons are major contributors of network inhibition in the neonatal hippocampus in-vivo

During development, neural network maturation is activity dependent. During the neonatal period, activity is provided by intermittent, spontaneous network activity patterns (SNAP) that occur independently of environment stimuli. Among the neurotransmitters that take part in neonatal development, the Gamma-amino-butyric acid (GABA) plays a pivotal role. GABAergic cells are the first to emerge the first to form functional synapses. GABA antagonists block hippocampal SNAPs in-vitro and alterations of GABAergic function dramatically impact cortical maturation. Based on these data, the traditional view is that the depolarizing action of GABA, a hallmark of immature networks in slice preparations, is at the core of developmental processes. However, in-vivo evidence for such depolarizing role is not clear, raising questions about the contribution of GABAergic neurons in-vivo. To address this issue we developed an in-vivo approach combining optogenetics and single-unit electrophysiology in non-anesthetized mice. This allowed us to both identify and manipulate hippocampal GABAergic cells while examining their influence on hippocampal SNAP. We found that, even during the first post-natal days, the net action of GABA is inhibitory, but not excitatory. This inhibitory action of GABA drastically increases after the second post-natal week.

neuroscience↗

bioRxiv2025

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↗

bioRxiv2022

Extrinsic control of the early postnatal CA1 hippocampal circuits

The adult CA1 region of the hippocampus produces coordinated neuronal dynamics with minimal reliance on its extrinsic inputs. In contrast, the neonatal CA1 is tightly linked to externally-generated sensorimotor activity but the circuit mechanisms underlying early synchronous activity in CA1 remain unclear. Here, using a combination of in vivo and ex vivo circuit mapping, calcium imaging and electrophysiological recordings in mouse pups, we show that early dynamics in the ventro-intermediate CA1 are under the mixed influence of entorhinal (EC) and thalamic (VMT) inputs. Both VMT and EC can drive internally-generated synchronous events ex vivo. However, movement-related population bursts detected in vivo are exclusively driven by the EC. These differential effects on synchrony reflect the different intrahippocampal targets of these inputs. Hence, cortical and subcortical pathways act differently on the neonatal CA1, implying distinct contributions to the development of the hippocampal microcircuit and related cognitive maps.

neuroscience↗

bioRxiv2021

The rapid developmental rise of somatic inhibition disengages hippocampal dynamics from self-motion

Early electrophysiological brain oscillations recorded in preterm babies and newborn rodents are initially mostly ignited by bottom-up sensorimotor activity and only later can detach from external inputs. This is a hallmark of most developing brain areas including the hippocampus, which in the adult brain, functions in integrating external inputs onto internal dynamics. Such developmental disengagement from external inputs is likely a fundamental step for the proper development of cognitive internal models. Despite its importance, the developmental timeline and circuit basis for this disengagement remain unknown. To address this issue, we have investigated the daily evolution of CA1 dynamics and underlying circuits during the first two postnatal weeks of mouse development using two-photon calcium imaging in non-anesthetized pups. We show that the first postnatal week ends with an abrupt shift in the representation of self-motion in CA1. Indeed, most CA1 pyramidal cells switch from activated to inhibited by self-generated movements at the end of the first postnatal week whereas the majority of GABAergic neurons remain positively modulated throughout this period. This rapid switch occurs within two days and follows the rapid anatomical and functional surge of local somatic GABAergic innervation. The observed change in dynamics is consistent with a two-population model undergoing a strengthening of inhibition. We propose that this abrupt developmental transition inaugurates the emergence of internal cognitive models.

neuroscience↗

bioRxiv2021

CA1 pyramidal cell diversity is rooted in the time of neurogenesis.

Cellular diversity supports the computational capacity and flexibility of cortical circuits. Accordingly, principal neurons at the CA1 output node of the hippocampus are increasingly recognized as a heterogeneous population. Their genes, molecular content, intrinsic morpho-physiology, connectivity, and function seem to segregate along the main anatomical axes of the hippocampus. Since these axes reflect the temporal order of principal cell neurogenesis, we directly examined the relationship between birthdate and CA1 pyramidal neuron diversity, focusing on the ventral hippocampus. We used a genetic fate-mapping approach that allowed tagging three groups of agematched principal neurons: pioneer, early- and late-born. Using a combination of neuroanatomy, slice physiology, connectivity tracing and cFos staining, we show that birthdate is a strong predictor of CA1 principal cell diversity. We unravel a subpopulation of pioneer neurons recruited in familiar environments with remarkable positioning, morpho-physiological features, and connectivity. Therefore, despite the expected plasticity of hippocampal circuits, given their role in learning and memory, the diversity of their main components is significantly predetermined at the earliest steps of development.

neuroscience↗

bioRxiv2019

Hippocampal hub neurons maintain unique functional properties throughout their lifetime

The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as hubs by orchestrating neuronal dynamics. However, their fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs signal a variety of network states, including the activation of local CA1 assemblies. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.

neuroscience↗

bioRxiv2019

Mutations of R882 in DNMT3A change flanking sequence preferences and cellular methylation patterns in AML

DNMT3A R882 mutations are frequently observed in AML including the abundant R882H and the rare R882C, R882P and R882S. Using deep enzymology we show here that the DNMT3A-R882H has more than 70-fold altered flanking sequence preferences when compared with wildtype DNMT3A. The R882H flanking sequence preferences mainly differ on the 3 side of the CpG site, where they resemble DNMT3B, while 5 flanking sequence preferences of R882H resemble wildtype DNMT3A, indicating that R882H behaves like a DNMT3A/DNMT3B chimera. Activities and flanking sequence preferences of R882C, R882P and R882S were determined as well. Genomic methylation patterns after expression of wildtype DNMT3A and R882H in human cells reflect the flanking sequence preferences. R882H specific hypermethylation in AML patients are correlated with R882H flanking sequence preferences. The hypermethylation events are accompanied by R882H specific misregulation of several genes with strong cancer connection in AML patients, which are potential downstream targets of R882H.

biochemistry↗