Kainate receptors modulate the microstructure of synchrony during dentate gyrus epileptiform activity.

Temporal Lobe Epilepsy (TLE) is the most common form of epilepsy in adults. In TLE, recurrent mossy fiber (rMF) sprouting from dentate gyrus granule cells (DGCs) forms an aberrant epileptogenic network between dentate granule cells (DGCs) that operates via ectopically expressed kainate receptors (KARs). It was previously shown that KARs expressed at the rMF-DGC synapses play a prominent role in epileptiform network events in TLE.

Clustering of vomeronasal receptor genes is required for transcriptional stability but not for choice.

Rodents perceive pheromones via vomeronasal receptors encoded by highly evolutionarily dynamic Vr and Fpr gene superfamilies. We report here that high numbers of V1r pseudogenes are scattered in mammalian genomes, contrasting with the clustered organization of functional V1r and Fpr genes. We also found that V1r pseudogenes are more likely to be expressed when located in a functional V1r gene cluster than when isolated.

mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice.

The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role in the regulation of the secretion of gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that a disruption of neuronal NO synthase (NOS1) activity underlies some forms of hypogonadotropic hypogonadism. Whole-exome sequencing was performed on a cohort of 341 probands with congenital hypogonadotropic hypogonadism to identify ultrarare variants in .

Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity.

In mammals, chemoperception relies on a diverse set of neuronal sensors able to detect chemicals present in the environment, and to adapt to various levels of stimulation. The contribution of endogenous and external factors to these neuronal identities remains to be determined. Taking advantage of the parallel coding lines present in the olfactory system, we explored the potential variations of neuronal identities before and after olfactory experience.

Paradoxical neuronal hyperexcitability in a mouse model of mitochondrial pyruvate import deficiency.

Neuronal excitation imposes a high demand of ATP in neurons. Most of the ATP derives primarily from pyruvate-mediated oxidative phosphorylation, a process that relies on import of pyruvate into mitochondria occuring exclusively via the mitochondrial pyruvate carrier (MPC). To investigate whether deficient oxidative phosphorylation impacts neuron excitability, we generated a mouse strain carrying a conditional deletion of MPC1, an essential subunit of the MPC, specifically in adult glutamatergic neurons.

Superior Colliculus to VTA pathway controls orienting response and influences social interaction in mice.

Social behaviours characterize cooperative, mutualistic, aggressive or parental interactions that occur among conspecifics. Although the Ventral Tegmental Area (VTA) has been identified as a key substrate for social behaviours, the input and output pathways dedicated to specific aspects of conspecific interaction remain understudied. Here, in male mice, we investigated the activity and function of two distinct VTA inputs from superior colliculus (SC-VTA) and medial prefrontal cortex (mPFC-VTA).

From immune to olfactory expression: neofunctionalization of formyl peptide receptors.

Variations in gene expression patterns represent a powerful source of evolutionary innovation. In a rodent living about 70 million years ago, a genomic accident led an immune formyl peptide receptor (FPR) gene to hijack a vomeronasal receptor regulatory sequence. This gene shuffling event forced an immune pathogen sensor to transition into an olfactory chemoreceptor, which thus moved from sensing the internal world to probing the outside world.

SARS-CoV-2 Receptors and Entry Genes Are Expressed in the Human Olfactory Neuroepithelium and Brain.

Reports indicate an association between COVID-19 and anosmia, as well as the presence of SARS-CoV-2 virions in the olfactory bulb. To test whether the olfactory neuroepithelium may represent a target of the virus, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2) and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express and .

Dynamic perceptual feature selectivity in primary somatosensory cortex upon reversal learning.

Neurons in primary sensory cortex encode a variety of stimulus features upon perceptual learning. However, it is unclear whether the acquired stimulus selectivity remains stable when the same input is perceived in a different context. Here, we monitor the activity of individual neurons in the mouse primary somatosensory cortex during reward-based texture discrimination.

Similarity and Strength of Glomerular Odor Representations Define a Neural Metric of Sniff-Invariant Discrimination Time.

The olfactory environment is first represented by glomerular activity patterns in the olfactory bulb. It remains unclear how these representations intersect with sampling behavior to account for the time required to discriminate odors. Using different chemical classes, we investigate glomerular representations and sniffing behavior during olfactory decision-making.

Transient Deregulation of Canonical Wnt Signaling in Developing Pyramidal Neurons Leads to Dendritic Defects and Impaired Behavior.

During development, the precise implementation of molecular programs is a key determinant of proper dendritic development. Here, we demonstrate that canonical Wnt signaling is active in dendritic bundle-forming layer II pyramidal neurons of the rat retrosplenial cortex during dendritic branching and spine formation. Transient downregulation of canonical Wnt transcriptional activity during the early postnatal period irreversibly reduces dendritic arbor architecture, leading to long-lasting deficits in spatial exploration and/or navigation and spatial memory in the adult.

Restoring wild-type-like CA1 network dynamics and behavior during adulthood in a mouse model of schizophrenia.

Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioral traits that are relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. We studied an animal model of the human 22q11 deletion syndrome, the mutation that represents the highest genetic risk of developing schizophrenia.

Evolution of immune chemoreceptors into sensors of the outside world.

Changes in gene expression patterns represent an essential source of evolutionary innovation. A striking case of neofunctionalization is the acquisition of neuronal specificity by immune formyl peptide receptors (Fprs). In mammals, Fprs are expressed by immune cells, where they detect pathogenic and inflammatory chemical cues.

Context- and Output Layer-Dependent Long-Term Ensemble Plasticity in a Sensory Circuit.

Sensory information is translated into ensemble representations by various populations of projection neurons in brain circuits. The dynamics of ensemble representations formed by distinct channels of output neurons in diverse behavioral contexts remains largely unknown. We studied the two output neuron layers in the olfactory bulb (OB), mitral and tufted cells, using chronic two-photon calcium imaging in awake mice.

Dense encoding of natural odorants by ensembles of sparsely activated neurons in the olfactory bulb.

Sensory information undergoes substantial transformation along sensory pathways, usually encompassing sparsening of activity. In the olfactory bulb, though natural odorants evoke dense glomerular input maps, mitral and tufted (M/T) cells tuning is considered to be sparse because of highly odor-specific firing rate change. However, experiments used to draw this conclusion were either based on recordings performed in anesthetized preparations or used monomolecular odorants presented at arbitrary concentrations.

Alteration of Nrp1 signaling at different stages of olfactory neuron maturation promotes glomerular shifts along distinct axes in the olfactory bulb.

Building the topographic map in the mammalian olfactory bulb is explained by a model based on two axes along which sensory neurons are guided: one dorsoventral and one anteroposterior. This latter axis relies on specific expression levels of Nrp1. To evaluate the role of this receptor in this process, we used an in vivo genetic approach to decrease or suppress Nrp1 in specific neuronal populations and at different time points during axonal targeting.

Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination.

Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination. We interfered with GABAergic inhibition of mitral and tufted cells (M/T cells), the principal neurons of the OB, by disrupting their potassium-chloride cotransporter 2 (Kcc2). Roughly, 70% of mice died around 3 weeks, but surviving mice appeared normal.

Large-scale transcriptional profiling of chemosensory neurons identifies receptor-ligand pairs in vivo.

In mammals, olfactory perception is based on the combinatorial activation of G protein-coupled receptors. Identifying the full repertoire of receptors activated by a given odorant in vivo, a quest that has been hampered for over 20 years by technical difficulties, would represent an important step in deciphering the rules governing chemoperception. We found that odorants induced a fast and reversible concentration-dependent decrease in the transcription of genes corresponding to activated receptors in intact mice.

Neuronal pattern separation in the olfactory bulb improves odor discrimination learning.

Neuronal pattern separation is thought to enable the brain to disambiguate sensory stimuli with overlapping features, thereby extracting valuable information. In the olfactory system, it remains unknown whether pattern separation acts as a driving force for sensory discrimination and the learning thereof. We found that overlapping odor-evoked input patterns to the mouse olfactory bulb (OB) were dynamically reformatted in the network on the timescale of a single breath, giving rise to separated patterns of activity in an ensemble of output neurons, mitral/tufted (M/T) cells.

Sensory-Evoked Intrinsic Imaging Signals in the Olfactory Bulb Are Independent of Neurovascular Coupling.

Functional brain-imaging techniques used in humans and animals, such as functional MRI and intrinsic optical signal (IOS) imaging, are thought to largely rely on neurovascular coupling and hemodynamic responses. Here, taking advantage of the well-described micro-architecture of the mouse olfactory bulb, we dissected the nature of odor-evoked IOSs. Using in vivo pharmacology in transgenic mouse lines reporting activity in different cell types, we show that parenchymal IOSs are largely independent of neurotransmitter release and neurovascular coupling.

The vomeronasal system mediates sick conspecific avoidance.

Although sociability offers many advantages, a major drawback is the increased risk of exposure to contagious pathogens, like parasites, viruses, or bacteria. Social species have evolved various behavioral strategies reducing the probability of pathogen exposure. In rodents, sick conspecific avoidance can be induced by olfactory cues emitted by parasitized or infected conspecifics.

Sensory-evoked LTP driven by dendritic plateau potentials in vivo.

Long-term synaptic potentiation (LTP) is thought to be a key process in cortical synaptic network plasticity and memory formation. Hebbian forms of LTP depend on strong postsynaptic depolarization, which in many models is generated by action potentials that propagate back from the soma into dendrites. However, local dendritic depolarization has been shown to mediate these forms of LTP as well.

A population of glomerular glutamatergic neurons controls sensory information transfer in the mouse olfactory bulb.

In sensory systems, peripheral organs convey sensory inputs to relay networks where information is shaped by local microcircuits before being transmitted to cortical areas. In the olfactory system, odorants evoke specific patterns of sensory neuron activity that are transmitted to output neurons in olfactory bulb (OB) glomeruli. How sensory information is transferred and shaped at this level remains still unclear.

Long term functional plasticity of sensory inputs mediated by olfactory learning.

Sensory inputs are remarkably organized along all sensory pathways. While sensory representations are known to undergo plasticity at the higher levels of sensory pathways following peripheral lesions or sensory experience, less is known about the functional plasticity of peripheral inputs induced by learning. We addressed this question in the adult mouse olfactory system by combining odor discrimination studies with functional imaging of sensory input activity in awake mice.