Intrinsic excitability

Various working memory (WM) models based on a diverse set of biologically plausible synaptic and neural plasticity mechanisms have been proposed. We show that these proposed short-term plasticity mechanisms may not necessarily be competing explanations, but instead yield interesting functional interactions on a wide set of WM tasks and enhance the biological plausibility of spiking neural network models of WM. While reductionist models (WM explained by one particular mechanism) are theoretically appealing and have increased our understanding of specific mechanisms, they are insufficient. WM mo

The external Globus Pallidus (GPe) is a central hub in the basal ganglia. This structure is composed mainly of GABAergic neurons, which are divided into two distinct subtypes called: prototypic (70%) and arkypallidal (ARKY: 20%) neurons differentiated by their molecular and electrophysiological signatures. ARKY neurons project exclusively to the striatum and send a stop signal that interrupt ongoing action, suggesting their key role in movement control. However, little is known about the contribution of ARKY neurons to the pathophysiology of Parkinson’s Disease (PD). Moreover, it has been rece

Studying human brain development has remained difficult as appropriate models lack. Recently, induced pluripotent stem cells (iPSC)-derived 3D brain organoids have been developed. They recapitulate the key aspects of human brain development such as the cellular complexity and functional properties of specific regions. Yet, longitudinal functional studies are sparse. During neurodevelopment in vivo, GABAergic inhibitory interneurons from the ventral cortex migrate to populate the dorsal part of the cortex enriched in glutamatergic excitatory neurons (Zhu et al. Neuron, 1999; Le et al., JBC, 200

Compulsive drug seeking is a key behavioral trait when studying transition to cocaine addiction in rodent models. Understanding how neurophysiological changes operate in circuits of compulsion, and searching for molecular markers to distinguish addictive vs. non-addictive individuals may help us to understand the mechanisms underlying cocaine addiction. Cocaine-evoked synaptic plasticity has been shown to correlate with addictive-like behavior in certain brain regions of the mesolimbic dopamine system. In the subthalamic nucleus (STN), specific oscillatory frequencies are associated to compuls

Achieving early diagnosis in Alzheimer's disease (AD) is a crucial objective in preclinical and clinical AD research, since it represents a therapeutic window during which interventions can be initiated before the onset of severe cognitive decline. Accumulation of amyloid-beta (Aß) in the prefrontal cortex is linked to rapid forgetting in this prodromal AD stage. Thus, early forgetting becomes a potential target for preclinical studies seeking to prevent/delay the onset of severe forms of AD. We used mouse models to identify early alterations in memory formation. Our findings indicate that Aβ1

…which store sleep need via their intrinsic excitability. Here, we test if and how dFB neurons incorporate this intrinsic account of sleep drive into their network activity. In vivo dFB neuron ensemble activity is rhythmic, with a peak at 0.2-1 Hz (measured via calcium imaging). The amplitude of these slow oscillations increases with sleep drive,

…integration of thalamic inputs and intrinsic

The subiculum is one of the most important brain structure in the hippocampal formation which has an essential role in forwarding the hippocampal information to different cortical and subcortical regions. Pyramidal cells are the principal cell type in the subiculum and based on their firing dynamics, they can be divided into regular and bursting phenotypes. Previously, functional characterization of these cells was mainly performed by using conventional electrophysiological methods (current steps). However, our research group uses advanced methods (dynamic clamp) to expose neurons to physiolog

Episodic memory enables us to recall specific events from daily life, pinpointing when and where they occurred. However, newly encoded episodic memories are typically fragile due to constant interference with ongoing experiences and require consolidation to form long-lasting memories. This consolidation process involves the replay of neuronal ensembles encoding recent experiences during sharp-wave ripples (SWRs) in the hippocampus. While substantial evidence supports the functional significance of neuronal replay during SWRs for memory consolidation, the cellular mechanisms determining which n

…at least in part, by changes in the intrinsic and synaptic properties of layer V/VI projecting neurons in aIC. Recent rodent studies have demonstrated that

Medial septal (MS) glutamatergic neurons expressing type 2 vesicular glutamate transporter (VGluT2) are active during theta oscillation and locomotor activity. Optogenetic activation of these neurons at theta frequencies (4-12 Hz) entrains hippocampal theta oscillation and sustains locomotion outlasting the stimulus duration. However, the specific cellular and circuit mechanisms responsible for initiating and sustaining MS VGluT2-driven persistent locomotion and associated hippocampal theta oscillations remain unclear. To address these questions, we optogenetically targeted glutamatergic neuro

Cannabis consumption, particularly among adolescents, has surged over the last decades. Adolescence is a critical period for brain development during which the prefrontal cortex (PFC) completes its maturation. There is strong evidence that the endocannabinoid system is a key regulator of brain development and of maturation of the PFC during adolescence. However, whether chronic cannabinoid receptor activation during this stage of development has long-term consequences for PFC function and associated behaviors remains unexplored. Here we show that repeated injection of cannabinoid receptor agon

…in ALS postulates that cortical hyperexcitability facilitates cell death. Previous research has identified the G4C2 hexanucleotide repeat expansion in the C9orf72 gene as the most common genetic cause of ALS; however, little is known about the contribution of the C9orf72 gene to neuronal excitability and synaptic dysfunction in the primary motor cortex. Thus, using C9orf72 knockout loss-of-function (C9-KO LOF) and gai

Withdrawal from opioids is associated with a highly aversive affective state, and avoidance of this state is a main reason people with opioid use disorder continue to use or relapse to opioids. Activity in the ventral pallidum (VP) is necessary for opioid relapse after withdrawal. Recent studies from our group and others have shown that glutamatergic VP neurons (VPGlu) constitute a unique subpopulation of VP neurons, and that VPGlu activity constrains reward seeking, particularly in decision-making tasks where negative consequences are associated with choosing a reward. However, how self-admin

Synapsin II (Syn II), a pivotal member of the synapsin family, is a synaptic vesicle-associated phosphoprotein which plays critical roles in regulating neurotransmitter release at both excitatory and inhibitory synapses within the central nervous system. Synapsins contribute significantly to synaptic plasticity and maintain the delicate balance between excitatory and inhibitory synaptic transmission. Notably, mutations in synapsins genes have been identified in forms of epilepsy with or without ASD. Syn II has been shown to interact with the presynaptic calcium channel P/Q, but the functional

Despite the limited knowledge on the safety of Cannabidiol (CBD) during pregnancy, pregnant women often use CBD to alleviate various pregnancy-related symptoms such as nausea, insomnia, anxiety, and chronic pain. While CBD can cross the human placenta, potentially affecting fetal development, the long-term consequences of prenatal CBD exposure remain poorly understood. The insular cortex (IC), a crucial brain region involved in multisensory and emotional processing, consists of two distinct subregions: the anterior IC (aIC), responsible for processing emotional and social signals, and the pos

…it remains to elucidate whether intrinsic neuronal excitability change upon visual stimuli. We show here that monocular deprivation for 10 days reduces the intrinsic excitability of dorsal LGN relay cells. Furthermore, dLGN neurons exhib

…a hypothesis according to which intrinsic excitability in neurons may be a survival mechanism to minimize toxic byproducts of the cell’s energy metabolism. In neurons, this toxicity can arise when mitochondrial ATP production stalls due to limited ADP. Under t

Can alterations in experience trigger different plastic modifications in neuronal structure and function, and if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry in the mouse olfactory bulb responsible for the earliest steps in odor processing. We induced experience-dependent plasticity in mice of either sex by blocking one nostril for one day, a minimally invasive manipulation that leaves the sensory organ undamaged and is akin to the natural transient blockage suffered during common mild rhinal infections. We found that such brief sensory d