Acetylcholine

The lateral septum (LS) integrates diverse subcortical and cortical inputs to generate appropriate affective behavioral responses related to fear, reward, social behaviors, and memory. Contrary to the medial septum (MS) the LS is considered an entirely GABAergic nucleus where neurons express a plethora of GABAergic markers in a partially overlapping manner. In this work, we describe a neglected and underappreciated neuronal subclass in the lateral septum expressing choline-acetyltransferase (ChAT), therefore named Lateral Septum Cholinergic Neurons (LSCNs). ChAT expressing neurons are immunohi

…linked to attention and phasic acetylcholine (Ach) release causally mediates performance in tasks involving monitoring for cues, cue detection, and cue-directed responding.We investigated the role of muscarinic and nicotinic ACh receptors (mAChRs and nAChRs) in attentional performance by applying systemic manipulations in adult male and female Sprague-Dawley rats during the Signal Detection Task. In this task,

The hippocampus is essential for spatial navigation and memory processes. Hippocampal pyramidal cells (PCs) often exhibit complex spike bursts (CSBs) that are driven by regenerative dendritic Ca2+ plateau potentials. These events can induce rapid synaptic plasticity and new place field (PF) formation in CA1PCs. CA3PCs also fire CSBs, and their PF-inducing CSBs were shown to be particularly prolonged (Li et al, bioRxiv). However, the dendritic mechanisms underlying such long-lasting events in CA3PCs remain unclear. In acute rat brain slices, we observed large heterogeneity among CA3PCs in CSB p

…densely innervate neocortex, releasing acetylcholine to regulate arousal, sensory processing and learning. Although the cholinergic system is one of the extensively studied neuromodulatory system, its impact on cortical processing remains unclear. Earlier studies have shown that BFCNs in rostral and caudal basal forebrain nuclei respond largely similar to reward and punishment despite their non-overlapping cortical projections, suggesting that BFCNs act as a unified broadcasting system. In contrast, more recent findings revealed dist

Internal states and behavior are associated with brain-wide changes in the activity of neuronal circuits. Such global shifts are believed to be implemented by changes in neuromodulatory tone. Neuromodulators originate from a few neurons and are released widely throughout the brain to alter the function of target circuits.The amygdala plays an essential role in the processing of emotional stimuli. Salience and synaptic alterations in this region are critical for emotional processing and learning. The amygdala is innervated by all major neuromodulators, yet we know little about the dynamics of n

Acetylcholine (ACh), a potent neuromodulator in the central nervous system, plays a pivotal role in visual processing, attention, and cognitive flexibility. Most of the studies have been using standard visual stimuli, but the advance of virtual reality (VR) tools is promising for better elucidating the dynamics of this neuromodulator in visually guided behaviors. The present study aims to explore the spatiotemporal activation of cortical cholinergic fibers during the presentation of a VR dynamic environment compared to standard visual stimuli using mesoscopic ACh imaging in awake mice.Choliner

Neuromodulatory systems, more specifically dopamine, noradrenaline, serotonin, and acetylcholine can dynamically change brain states and rapidly alter information processing of large number of neurons. Therefore, they can play a crucial role in cognitive functions, including learning and memory, and are accordingly severely implicated in neurodegenerative diseases. Interestingly, neuromodulatory systems often regulate seemingly overlapping cognitive processes and show similar modes of action. To reveal possible synergistic or antagonistic relations and to better understand the exact role of th

A hallmark of Alzheimer’s disease (AD) pathology is amyloid plaques which can lead to neuroinflammation, cellular dysfunctions as well as altered neuronal activity. Both AD patients and mouse models exhibit abnormal neural oscillations, including altered gamma oscillations, hippocampal sharp wave-ripples (SWRs) and cortical sleep spindles. Although these oscillations play a role in memory formation and consolidation, it remains poorly understood how abnormal oscillations relate to novel experiences. Here we show that deficits in SWRs are experience-dependent in an AD mouse model. We performed

Striatal dopamine (DA) and acetylcholine (ACh) play key roles in reward prediction signalling and goal-directed behaviour. Midbrain DA neurons increase their firing in response to unexpected rewards or reward-predicting cues, while striatal cholinergic interneurons exhibit coincident burst-pause activity. Striatal DA and ACh also reciprocally regulate each other’s release with ACh modulating DA release through axonal nicotinic acetylcholine receptors (nAChRs). Activation of nAChRs can drive DA release but also generate strong short-term depression (STD) of subsequent DA release, not arising fr

We aimed to investigate the role of dopamine (DA), acetylcholine (ACh), norepinephrine (NE) and serotonin (5-HT) in associative learning and the correlation of their release with the reward prediction error (RPE). To address this, we trained mice on a sound detection Pavlovian conditioning task with a 50% reward schedule that allowed examining clean representations of postivite (rewarded trials) and negative RPE (reward omission trials), while we measured DA, ACh, NE and 5-HT release by fiber photometry. Behavioral updating of value representations based on the outcome of the previous trial wa

…Cholinergic neurons, which release acetylcholine (ACh), are known to enhance attention and their pathophysiology is associated with disorders such as Alzheimer’s disease and epilepsy. Nicotinic acetylcholine receptors (nAChRs) are activated by the cholinergic system and modulate neuronal excitability. Therefore, understanding nAChR mediated synaptic neurotransmission will allow us to better understand how the activity of neurons are precisely controlled

…transmitters norepinephrine (NE) or acetylcholine (ACh), (2) Ca2+ activity of local cortic

AimStriatal cholinergic interneurons (CINs) use both acetylcholine (ACh) and glutamate (Glu) to regulate the striatal network. CINs express vesicular transporters for acetylcholine (VAChT) and Glu (VGLUT3). We recently demonstrated, using super resolution STimulated Emission Depletion microscopy (STED) microscopy, that part of cholinergic synaptic vesicles (SVs) contains both VAChT and VGLUT3, whereas others express only VAChT or only VGLUT3. CINs SVs are thus able to release either ACh or Glu or both. However, the link between neurotransmitters accumulation into SVs and their final exocytosis

…acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT) and acetylcholinesterase (AChE), respectively. Presynaptic activity and nerve-induced muscle contraction regulate ACh release through muscarinic ACh autoreceptors (mAChRs). We previously identified a complex protein network including M1 and M2 mAChRs and multiple kinases that regulate ACh release at the NMJ. The aim of this w

…striatal neuromodulators including acetylcholine (ACh), GABA and adenosine, which regulate the amplitude and activity-sensitivity of DA release. Adrenoceptors are expressed throughout the striatum but their role, and that of norepinephrine (NE) as a potential striatal neuromodulator, is poorly understood. Given only a sparse norepinephrinergic input of the striatum but the dense innervation by DA, the endogen

…Specifically, acetylcholine has frequently been pro

…balance between striatal dopamine and acetylcholine neuromodulators. The main source of acetylcholine in the striatum are cholinergic interneurons (CINs) which express heteromeric nicotinic acetylcholine receptors (nAChRs) containing beta2 subunit (beta2* nAChRs). Our group has previously shown that the deletion of beta2* nAChRs in CINs leads to behavioural changes in mice and to alterations of Fos expression in the striatum. Therefore, we hypothesize that the beta2 deletion leads to a decrease of CINs'

The striatum is the predominant input structure of the striatum, receiving converging glutamatergic and GABAergic inputs from cortical and subcortical regions. It also receives modulatory input from midbrain dopamine neurons which has been shown to be critical for motor initiation, learning and reward. Additionally, the striatum also receives serotonergic input with one third of serotonergic neurons projecting from the dorsal raphe nucleus (DRN) to the striatum. Here, we studied the impact of 5-HT on the interactions between Cholinergic interneurons (ChINs). ChINs are key modulators of striata

Acetylcholine (ACh) release in the medial prefrontal cortex (mPFC) is essential to numerous cognitive functions and disruptions of cortical ACh transmission has been implicated in several disorders, including attentional deficit hyperactivity disorder (ADHD), Alzheimer’s disease or schizophrenia and addictive behavior. Similarly in rodents, it has been shown that cognitive functions rely on the mPFC neuronal activity and that ACh release can modulate mPFC neuronal activity thereby altering cognitive behaviors, in particular attention. The main ACh innervation of mPFC originates in basal forebr

…by two neuromodulators, dopamine and acetylcholine, whose levels are among the highest in the brain. Yet, how dopamine and acetylcholine interact to facilitate adaptive perceptual decision-making is unclear. To address this question, we characterized dopamine and acetylcholine release in the dorsolateral

Acetylcholine is a neurotransmitter and neuromodulator that critically modulates cognition. We have shown that acetylcholine activates axonal muscarinic receptors in hippocampal dentate gyrus granule neurons to persistently lower the action potential (AP) threshold and enhance neuronal excitability1. This was due to a sustained increase in T-type Ca2+ channel activity resulting in elevated basal Ca2+ levels which inhibited KV7 channels. The intracellular mechanism coupling axonal muscarinic receptors to T-type Ca2+ channels remains unknown. We investigated this by making electrophysiological r

…experimental evidence showing that acetylcholine inputs throughout the cortex form the backbone for a global signal, that presents the main characteristic of an unsigned reinforcement prediction error computation : modulation of the reinforcement response by expectation and coding of predictive cues. We show that this gl

The striatum is crucial for motor control and reinforcement learning. The striatum has only 1% fast-spiking interneurons (FSI) which constitute feedforward inhibition (FFI). Therefore, striatal neurons receive a high degree of shared FFI, which makes the striatum a unique network in the brain. Here we ask, what role such high shared FFI may play in striatal function besides inducing synchrony. We found that with highly shared connectivity FSIs increase the trial-by-trial variability of striatal responses. Moreover, when the striatum is driven by correlated inputs, FSIs decorrelate the response

…experiments have shown that acetylcholine plays a fundamental role in cortical activation via muscarinic receptors. However, muscarinic receptors have diverse and sometimes contradictory effects in different cell types and cortical layers, and as a result the mechanism(s) of this activating influence remain unclear. Computational models have predicted that increasing excitatory neuron excitability (an M1-type muscar