Topic: chemogenetic inhibition

The nervous system must perceive and learn durations to guide adaptive behavior. Prior work to investigate the neural substrates of interval timing has focused largely on relatively simple timing tasks whereby subjects learn to discriminate and reproduce the duration of events occurring at a single fixed interval. Although episodic memory requires accurate temporal coding and is mediated by structures in the medial temporal lobe (MTL), including the medial entorhinal cortex (MEC), a well-established role for MTL circuits in interval timing behavior is conspicuously lacking. MEC seems well-suit

Locomotor behaviors are composed of ordered transitions between motor states required to produce a functional outcome. However, the circuit mechanisms by which the brain generates a sequential ordering of motor actions for constructive behavioral output, particularly in freely-behaving animals, is largely unknown. With 302 neurons within a well-defined connectome and a library of genetic tools, complex yet discernible behaviors, and recent advances in brain-wide imaging, the nematode Caenorhabditis elegans offers a unique opportunity to study how the brain generates behavior. To better underst

The neuronal population of the striatum is primarily composed of medium spiny projecting neurons (MSNs), with only a small percentage (around 5% in mice) being locally projecting neurons or interneurons. Despite their low numbers, interneurons play a crucial role in regulating the flow of information within the striatum and to other brain nuclei, thereby having significant implications for motor control and cognition.We recently identified one of the most abundant populations of GABAergic interneurons in the striatum that express Pthlh and varying levels of Pvalb, which correlates with intrins

Recent evidence suggests that the cerebellar hemispheres are in a unique position to contribute to motor planning via cortico-cerebellar loops. However, it is unknown how the dynamics of preparatory activity relate to the functional parcellation of the cerebellar cortex. We used mesoscale widefield calcium imaging to study molecular layer interneuron and Purkinje cell dendritic Ca2+ activity in Simplex, Crus I and Crus II during a targeted lick-interception task. We identified independent spatial sources of Ca2+ activity in interneurons and Purkinje cell dendrites using non-negative matrix fac

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics, which are sudden, rapid, recurrent, non-rhythmic movements. The TS is also accompanied by cognitive and emotional dysfunctions such as obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). Dysfunction of the cortico-basal ganglia-thalamocortical circuits has been suggested to induce these symptoms in TS patients, but the details of neuronal mechanisms underlying tic disorders remain unknown. In this study, we generated drug-induced tic model mice by unilateral local

Locomotion initiation and speed control are dependent on activity in the Mesencephalic Locomotor Region (MLR). In mammals the MLR is constituted of glutamatergic neurons in the pedunculopontine nucleus (PPN) and cuneiform nucleus (CnF) that act together to control locomotion speed. To further understand their contribution in the context of sensory evoked locomotor behaviour, we asked how visually evoked locomotor escape responses in mice are modulated by MLR. To evoke natural escape we used innate looming responses. Using chemogenetic inhibition of targeted Vglut2+ glutamatergic neurons in PPN

The habenula is a phylogenetically conserved bilateral brain structure known to modulate negative emotions. Hemispheric asymmetry in cortical areas plays a key role in behavior and cognition. Although habenular asymmetry is prominent in several vertebrate species, there is little evidence for left-right asymmetry in the mammalian habenula. To investigate the asymmetry in synaptic transmission in the medial habenula (MHb) to the interpeduncular nucleus (IPN) pathway in mice, we performed targeted electrical stimulation of left or right MHb-derived axons in acute slices. We discovered that the p

Stress is a physiological adaptive response towards physical and psychological stressors that can have profound impact on appetite. In addition to suppressing food intake, stress has also been shown to reduce reward seeking and cue-induced appetitive behaviours. Previous studies show that stress activates hindbrain nucleus of the solitary tract (NTS) neurons and NTS neurons have been implicated in stress-induced suppression of food intake. However, whether NTS neurons mediate the effects of stress on cue-induced appetitive behaviours are unclear. Using behavioural, pharmacogenetic and neural m

Social defence is an essential behaviour for social animals. It allows the existence of winners and losers in agonistic encounters, without deaths, promoting the group's stability. As for other aversive contexts, the environmental cues (e.g. the distance to the aggressor) are essential for a proper expression of defence. Understanding how the brain processes these cues, associating them with other stimuli and defining the defensive response, is a fundamental step towards a better comprehension of the neural bases of social defence. Previous work suggests that, in C57Bl/6 mice, a septo-hippocam

Persistence is a key characteristic of memory that relies on systems consolidation, a process classically defined as the gradual transfer of information from the hippocampus to the cortex for long-term memory storage. However, the underlying molecular mechanisms are unknown. DNA methylation can act as a long-term regulatory signal, therefore being a prime candidate to regulate memory duration and stabilisation within engrams– the physical substrate of a memory.Using contextual fear conditioning (CFC) and engram tagging tools in mice, we showed that reactivation of cortical engrams reflects sys

It is widely believed that synaptic transmission in the hippocampus plays a crucial role in formation of contextual memories. Data obtained in our laboratory implies that PSD-95 (postsynaptic density protein 95)-dependent synaptic plasticity in dCA1 area is required for updating of contextual fear memory.To check how inactivation of dCA1 area affects contextual fear memory extinction, we stereotactically injected the adenoviral vectors (AAVs) encoding DREADD receptor hM4 [AAV2.1:hSyn_hM4_mCherry]. Next we trained mice in contextual fear conditioning (CFC). We found that chemogenetic inhibition

It is well known that the state of hunger can modulate hormones and hypothalamic neural circuits to drive food-seeking behavior and consumption. While the olfactory sense is critical to foraging, the role of the olfactory cortex in regulating food learning and preference is unclear. The anterior piriform cortex (APC) is located one synapse downstream of the olfactory bulb and is an important olfactory structure for odor discrimination, perception, and memory. Here, we investigated whether acute fasting in mice can alter an odor-guided foraging behavior and how it can alter neurons and synapses

Stroke is a preeminent contributor of the global burden of diseases. Hypothermia, among other therapeutic approaches, has been proposed to promote neural survival after stroke, yet the physiological cooling remains ineffective and induces collateral side effects. The thermoregulatory mechanisms are under the control of neuronal identities that connect peripheral signals of the central nervous system, which are predominantly conveyed into the hypothalamus. Here, we aimed to identify a thermoregulatory neuronal subpopulation located at the dorsomedial hypothalamus (DMH) and investigate the DMH-p