Chemogenetics

Neuronal networks require precise coordination of excitatory and inhibitory synaptic connectivity to function properly. Regulation of parvalbumin-positive (PV+) interneuron activity is especially important for network function, and changes in PV+ interneuron activity correlate with an animal’s performance in learning tasks. Previously, changes in PV+ interneuron connectivity have been shown to regulate excitatory pyramidal cell activity. However, the mechanism via which PV+ interneurons control their own activity remains unknown. Here we used a chemogenetic approach to change the activity of P

The interaction of the hippocampus and amygdala, crucial for the formation of emotional memories, may play a central role in the pathophysiology of posttraumatic stress disorder (PTSD). However, with amygdala hyperactivity regarded as a hallmark of PTSD, it is still not clear whether amygdala hyperresponsiveness before a traumatic event is a predisposing factor for the development of PTSD or is an acquired condition upon trauma. To address this question, in the current study, we explore the effect of heightened amygdala activity on anxiety and fear memory in the formation of hippocampal fear m

…on sleep physiology in rats using chemogenetics.Rats were injected with AAVs to express hM3Dq in either the mediodorsal (MDT), ventroposterior (VPT) or ventromedial thalamus (VMT). Electrodes were implanted in front

The vestibular system plays a pivotal role in tracking head direction for effective navigation in complex environments. We hypothesize that the decline in navigational ability observed with aging is closely linked to the deterioration of a key ascending vestibular pathway in the head-direction network. With cre-dependent viruses for both anterograde and retrograde tracings, we discovered in mice a previously unreported direct pathway from the medial vestibular nucleus (MVN) to the dorsal tegmental nucleus (DTN), supplementing the conventional indirect pathways via the nucleus prepositus hypogl

…used calcium imaging, optogenetics, chemogenetics, in association with multiple hippocampus-dependent learning tasks to investigate their contribution to memory engrams over time

Early episodic and contextual memories are forgotten despite their distinct impact on personality development and future behaviour. This phenomenon, termed infantile amnesia, is widely seen in humans and is conserved across other altricial species. In previous years it has become evident that infant memories are stored through the plasticity of neuronal ensembles, forming engrams that remain present in the brain in a latent state once forgotten. Recently, it has been shown that alterations in brain development caused by maternal immune activation (MIA) lead to infant memory retention in male o

Memories have been suggested to be stored in groups of neurons known as neuronal ensembles, or “engrams”, and neuroplasticity is believed to be the underlying mechanism that allows the formation or remodeling of these ensembles, thus allowing memory modifications. Critically, the hippocampus has been described as a central hub for neuronal ensembles. In the context of fear memory, the representation of the hippocampal neuronal ensemble has been characterized, while little is known about the neuronal ensemble within the hippocampus and the upstream circuits in spatial learning and memory. With

The subthalamic nucleus (STN) holds a strategic position in the basal ganglia circuit, controlling both motor and non-motor functions. Alterations in its neuronal activity have been shown to be involved in the pathophysiology of Parkinson’s disease (PD). In addition to its classical intra-basal ganglia connections, STN neurons also project to several cortical areas. However, the degree of involvement of these subthalamo-cortical projections in motor and non-motor functions, and in the pathophysiology of PD has never been characterized.The aim of this study was to investigate the effects of inh

The hippocampus plays an integral role in episodic memory, primarily through neurons in the CA1 subfield. Beyond the well-established canonical circuitry, the CA2 region is implicated in social memory. Notably, there are monosynaptic connections from CA2 that innervate CA1, the functional relevance of which remains relatively unknown. Our study aims to investigate how these CA2-CA1 connections can modulate the maintenance of functional plasticity models, such as long-term potentiation (LTP) and long-term depression (LTD), within the Schaffer collateral (SC)-CA1 synapses. Subthreshold stimulati

Rat sexual behavior is a natural reward behavior that offers the unique opportunity to control the timing of exposure for the first time. A certain level of sexual motivation is required to turn desire into approach, leading to copulation and ejaculation. A coordinated transition between these phases is essential for a successful completion of the cycle. Moreover, gaining sexual experience enables a more efficient sexual cycle by markedly improving the patterning of behavioral responses. The neural regulation of this behavior and the transitions between phases requires different neurons to con

Neuronal circuits located in the midbrain play a critical role in controlling defensive behavior. However, it is still elusive how different neuron types contribute to distinct behavioral outcomes during the presence of threat. In this study, we investigated neurons expressing vasoactive intestinal polypeptide (VIP) in the ventral periaqueductal gray (PAG) and dorsal raphe nucleus in mice. These VIP-expressing neurons also expressed tyrosine hydroxylase (TH), a marker for dopaminergic cells. Using viral tracing conducted in Vip-Cre mice, we observed that these VIP-expressing neurons innervated

The nanoscale arrangement of chemical synapses is thought to be critical for establishing synapse strength but whether this arrangement is sensitive to changes in in vivo activity is not known. Pyramidal neurons in the cortex receive a multitude of excitatory and inhibitory inputs that determine the generation of the action potential (AP) at the axon initial segment (AIS). Chandelier cells (ChCs), a GABAergic interneuron subtype, targets the AIS of pyramidal neurons through axo-axonic synapses and is therefore thought to strongly modulate neuronal output. We used super-resolution microscopy (S

…behaviors.We combined opto-, chemogenetics and calcium imaging

…Taking advantage of chemogenetics, we modulated the activity of parvalbumin (PV)-

Consolidation of salient experiences to form memories rely on precise coupling of high frequency neural network events between hippocampus and neocortex. Within these events, reactivation of subpopulations of neurons is believed to strengthen connections within and between networks. We have previously shown that cue-specific reactivation occurs in postrhinal cortex during learning of a visual association task. Moreover, recent work suggests a role for parvalbumin-expressing (PV) inhibitory interneurons in consolidation by synchronizing hippocampal and cortical activity. We therefore hypothesiz

…Here, we combine chemogenetics, rsfMRI and electrophysiology to causally probe

…combining calcium imaging and opto- or chemogenetics in freely behaving mice, we investigated functions

…ablated DRN 5-HT neurons using chemogenetics and assessed different types of anxiety-lik

…Here, we employed chemogenetics to selectively modulate the IL during reinstatement of cocaine-related behaviours in the conditioned place preference (CPP) model. To this aim, C57BL/6J mice (N = 28) received intra-IL microinjections of adeno-associated viral vectors containing either silencing (AAV5-CaMKIIα-hM4Di-mCherry) or stimulatory (AAV5-CaMKIIα-hM3Dq-mCherry) designer recepto

Neuronal ensembles that hold specific memories (memory engrams), are defined as enduring physical and/or chemical change in a neural network that is the result of neuronal activation by episodic stimuli [1] Engram cells have been identified in multiple brain regions, including the hippocampus, amygdala, thalamus, and cortex It has been hypothesized that these distributed engrams are functionally connected [2] This neural network can be specifically reactivated, resulting in the recall of the original memory [3]However, how the interaction among multiple regions facilitates the consolidation, o

Contextual fear learning is a mental process, during which an originally neutral context becomes associated with a threat. Previous data have shown that one of the main controlling units of the defensive system, the central amygdala (CeA) is an active participant of contextual fear learning. Recently we showed that vasoactive intestinal polypeptide (VIP)-expressing neurons in the periaqueductal gray and dorsal raphe that innervate the CeA play a role in contextual fear acquisition, but not in the recall. As the primary source of contextual information is the hippocampus, we aimed to uncover th

…marmoset, employing pathway-specific chemogenetics, neuroimaging, neuropharmacology and beh

Motivational drives are internal states that can be different even in similar interactions with external stimuli. Curiosity as the motivational drive for novelty-seeking and investigating the surrounding environment is for survival as essential and intrinsic as hunger. Curiosity, hunger, and appetitive aggression drive three different goal-directed behaviors—novelty seeking, food eating, and hunting— but these behaviors are composed of similar actions in animals. This similarity of actions has made it challenging to study novelty seeking and distinguish it from eating and hunting in nonarticul

…with transgenic mouse lines and chemogenetics to manipulate neural circuit function. We are interested in three major areas. First, we work to understand how neurons in the retina are functionally connected. Second we are studying how light-adaptation and circadian rhythms alter visual processing in the retina. Finally, we are working to understand the mechanisms of retinal deg