Biology subjects

Carleton, A.

Publications and source records attributed to Carleton, A..

12 recordsLinked to original sources

bioRxiv2025

Nose-to-ground distance drives the evolution of mammalian odorant receptor repertoire size

The largest protein-coding gene family in mammals encodes the repertoire of chemosensors responsible for detecting odorants, namely odorant receptors (ORs). OR gene numbers vary widely across species, ranging from a few hundred in some primates to over two thousand in elephants. Here, we report that proximity to the ground, a rich source of olfactory cues, has broadly influenced the evolutionary expansion and contraction of OR mammalian repertoires. Analyzing 158 terrestrial mammalian species, we find a strong inverse correlation between nose-to-ground distance and the number of functional OR genes. In contrast, no significant association was found between nose-to-ground distance and the size of other chemoreceptor families, including vomeronasal and bitter-taste receptors. As a case study, we examined OR repertoire divergence between giraffe and okapi lineages, revealing that differential rates of gene duplication and pseudogenization resulted in giraffes possessing 25% fewer ORs than okapis. Together, our findings suggest that the chemical complexity of the olfactory environment has shaped the evolution of OR repertoires, providing new insights into gene family size and diversification in mammals.

evolutionary biology↗

bioRxiv2024

A spatial single-cell atlas of the claustro-insular region uncovers key regulators of neuronal identity and excitability

The claustro-insular region is an evolutionarily conserved and extensively interconnected brain area, critical for functions such as attention, cognitive flexibility, interoception, and affective processing. Despite its importance, its cellular composition and organization remain poorly characterized, hindering a comprehensive understanding of the mechanisms underlying its diverse functions. By combining single-cell RNA sequencing and spatial transcriptomics, we created a high-resolution atlas of this region in mice, uncovering distinct neuronal subtypes and unexpected complexity. Leveraging this atlas, we investigated the role of NR4A2, a neuropsychiatric risk factor expressed in several claustro-insular neuronal subtypes. In an Nr4a2 haploinsufficiency model, we found that only claustrum neurons exhibited shifts in molecular identity. This identity shift, which involved the activation of a transcription factor cascade, was associated with alterations in neuronal firing activity. Our findings provide new insights into the cellular architecture of the claustro-insular region and highlights Nr4a2 as a master regulator of its components identities.

neuroscience↗

bioRxiv2024

The claustrum is critical for maintaining working memory information

Working memory (WM) enables the mammalian brain to temporarily store and manipulate information, supporting cognitive tasks and communication processes1,2. Rather than depending on a single specialized area, WM is thought to operate through a distributed network spanning cortical and subcortical regions3-5. A dedicated WM storage area would likely require broad reciprocal connections with various cortical regions to accommodate the diverse range of information WM retains. The claustrum (CLA), with its extensive bidirectional connections to the neocortex6-9, presents a compelling candidate for such a role. Here, we examined the involvement of the CLA in WM processes by recording CLA neuronal activity in mice engaged in olfactory and tactospatial delayed non-match-to-sample WM tasks. We identified cue- selective and delay-specific neurons in the CLA that maintained activity for tens of seconds after the stimulus presentation ended. Additionally, population activity in the CLA allowed for decoding of cue identity post-stimulus, although this signal gradually declined over time, aligning with animal behavior. Remarkably, both chemo- and optogenetic inhibition of CLA neurons severely impaired WM performance across multiple types of stored information, highlighting the CLAs critical role during both cue encoding, delay periods, and target comparison phases. These findings challenge the view that no single brain area is essential for WM storage and support a role for the CLA as an essential WM storage hub.

neuroscience↗

bioRxiv2024

A toolbox for genetic targeting of the claustrum

The claustrum (CLA), a subcortical nucleus in mammals, essentially composed of excitatory projection neurons and known for its extensive connections with the neocortex, has recently been associated with a variety of functions ranging from consciousness to impulse control. However, research on the CLA has been challenging due to difficulties in specifically and comprehensively targeting its neuronal populations. In various cases, this limitation has led to inconsistent findings and a lack of reliable data. In the present work, we describe the expression profile of the Smim32 gene, which is almost exclusively transcribed in excitatory neurons of the CLA and the endopiriform nucleus, as well as in inhibitory neurons of the thalamic reticular nucleus. Leveraging this unique expression pattern, we developed a series of Cre- and Flippase-expressing knockin and BAC transgenic mouse lines with different expression profiles. With these novel tools in hand, we propose new standards for the interrogation of CLA function.

neuroscience↗

bioRxiv2023

The claustrum drives large-scale interactions of cortical circuits relevant to long-term memory

The consolidation and recall of episodic memories rely on distributed cortical activity. The claustrum, a subcortical structure reciprocally connected to most of the cortex, may facilitate inter-areal communication necessary for these processes. We report here that the functional inhibition of claustral projection neurons affects directional interactions and the coordination of oscillatory neuronal patterns in the fronto-parietal network. Moreover, the inhibition of these neurons has a detrimental effect on concurrent oscillatory events relevant to the consolidation of contextual fear memory. Last, we demonstrate that biasing the directional flow of information between the latter two cortical areas enhances the retrieval of a remote contextual memory. We propose that the claustrum orchestrates inter-areal cortical interactions relevant to contextual memory processes by affecting the latency of neuronal responses. One-Sentence SummaryThe claustrum coordinates inter-areal cortical activity.

neuroscience↗

bioRxiv2021

Transcriptional adaptation of sensory neurons to GPCR identity and activity

Sensory adaptation is critical to extract information from a changing world. Taking advantage of the extensive parallel coding lines present in the olfactory system, we explored the potential variations of neuronal identities before and after olfactory experience. We found that at rest, the transcriptomic profiles of olfactory sensory neuron populations are already highly divergent, specific to the olfactory receptor they express, and are surprisingly associated with the sequence of these latter. These divergent profiles further evolve in response to the environment, as odorant exposure leads to massive reprogramming via the modulation of transcription. Adenylyl cyclase 3, but not other main elements of the olfactory transduction cascade, plays a critical role in this activity-induced transcriptional adaptation. These findings highlight a broad range of sensory neuron identities that are present at rest and that adapt to the experience of the individual, thus providing a novel layer of complexity to sensory coding.

neuroscience↗

bioRxiv2020

The claustrum-medial prefrontal cortex network controls attentional set-shifting

In various mental disorders, dysfunction of the prefrontal cortex contributes to cognitive deficits. Here we studied how the claustrum (CLA), a nucleus sharing reciprocal connections with the cortex, may participate in these cognitive impairments. We show that specific ensembles of CLA and of medial prefrontal cortex (mPFC) neurons are activated during a task requiring cognitive control such as attentional set-shifting, i.e. the ability to shift attention towards newly relevant stimulus-reward associations while disengaging from irrelevant ones. CLA neurons exert a direct excitatory input on mPFC pyramidal cells, and chemogenetic inhibition of CLA neurons suppresses the formation of specific mPFC assemblies during attentional set-shifting. Furthermore, impairing the recruitment of specific CLA assemblies through opto/chemogenetic manipulations prevents attentional set-shifting. In conclusion, we propose that the CLA controls the reorganization of mPFC ensembles to enable attentional set-shifting, emphasizing a potential role of the CLA-mPFC network in attentional dysfunctions.

neuroscience↗

bioRxiv2020

SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium

Various reports indicate an association between COVID-19 and anosmia, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, 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 ACE2 and TMPRSS2. We then observed that the ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.

neuroscience↗

bioRxiv2019

Dynamic encoding of perceptual features 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 monitored the activity of individual neurons in the mouse primary somatosensory cortex in a reward-based texture discrimination task. We tracked their stimulus selectivity before and after changing reward contingencies, which allowed us to identify various classes of neurons. We found neurons that stably represented a texture or the upcoming behavioral choice, but the majority was dynamic. Among those, a subpopulation of neurons regained selectivity contingent on stimulus-value. These value-sensitive neurons forecasted the onset of learning by displaying a distinct and transient increase in activity, depending on past behavioral experience. Thus, stimulus selectivity of excitatory neurons during perceptual learning is dynamic and largely relies on behavioral contingencies, even in primary sensory cortex.

neuroscience↗

bioRxiv2019

Superior Colliculus to VTA pathway controls orienting behavior during conspecific interaction.

Social behaviours characterize cooperative, mutualistic aggressive or parental interactions that occurs among conspecifics. Although several neuronal substrates of social behaviour have been identified, whether defined circuits are dedicated to specific aspect of conspecific interaction is still an open question. Ventral Tegmental Area (VTA) contributes to the rewarding properties of conspecific interaction. However, how information related to conspecifics are conveyed to the VTA is still largely unknown. In this study, we identified a population of Superior Colliculus (SC) neurons projecting to the VTA which increase their activity before conspecific interaction and control orienting response towards unfamiliar conspecifics. Finally, we show that SC inputs target a subpopulation of Dopamine (DA) neurons within the VTA that in turn project to dorsolateral striatum (DLS). Our work supports the hypothesis that specialized sub-circuits are dedicated to process different aspect of social interaction.

neuroscience↗

bioRxiv2018

Similarity and strength of glomerular odor representations define neural metric of sniff-invariant discrimination time

The olfactory environment is first represented by glomerular activity patterns in the olfactory bulb. It remained unclear, how these activity patterns intersect with sampling behavior to account for the time required to discriminate odors. Using different classes of volatile stimuli, we investigated glomerular activity patterns and sniffing behavior during olfactory decision-making. Mice discriminated monomolecular odorants and binary mixtures on a fast time scale and learned to increase their breathing frequency at a fixed latency after trial initiation, independent of odor identity. Relative to the increase in breathing frequency, monomolecular odorants were discriminated within 10-40 ms while binary mixtures required an additional 60-70 ms. Intrinsic imaging of odor-evoked glomerular activity maps in anesthetized and awake mice revealed that the Euclidean distance between glomerular patterns elicited by different odors, a measure of similarity and activation strength, was anti-correlated with discrimination time. Therefore, the similarity of glomerular patterns and their activation strengths, rather than sampling behavior, define the extent of neuronal processing required for odor discrimination, establishing a neural metric to predict olfactory discrimination time.

neuroscience↗

bioRxiv2017

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

Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioural traits relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. Here we studied an animal model of the 22q11 deletion syndrome, which is the highest genetic risk to develop the pathology. We report a desynchronization of hippocampal neuronal assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing parvalbumin interneuron excitability with pharmacological or chemogenetic approaches is sufficient to restore wild type-like network dynamics and behaviour during adulthood. In conclusion, our data provide mechanistic insights underlying network dysfunction relevant to schizophrenia and demonstrate the potential of reverse engineering in fostering new therapeutic strategies to alleviate the burden of neurodevelopmental disorders.

neuroscience↗