scholarly journals Dissociable roles of central striatum and anterior lateral motor area in initiating and sustaining naturalistic behavior

2020 ◽  
Author(s):  
Victoria L. Corbit ◽  
Sean C. Piantadosi ◽  
Jesse Wood ◽  
Grace Liu ◽  
Clare J.Y. Choi ◽  
...  
Keyword(s):  
Motor Behavior ◽  
Motor Area ◽  
Grooming Behavior ◽  
Calcium Activity ◽  
Behavioral Selection ◽  
Optogenetic Stimulation ◽  
Corticostriatal Circuits ◽  
Cortical Inputs ◽  
Stimulation Of

AbstractAlthough much is known about how corticostriatal circuits mediate behavioral selection, most previous work has been conducted in highly trained animals engaged in instrumental tasks. Understanding how corticostriatal circuits mediate behavioral selection and initiation in a naturalistic setting is critical to understanding how the brain chooses and executes behavior in unconstrained situations. Central striatum (CS), an understudied region that lies in the middle of the motor-limbic topography, is well-poised to play an important role in these processes since its main cortical inputs (Corbit et al., 2019) have been implicated in behavioral flexibility (lateral orbitofrontal cortex (Kim and Ragozzino, 2005)) and response preparation (anterior lateral motor area, ALM) (Li et al., 2015), However, although CS activity has been associated with conditioned grooming behavior in transgenic mice (Burguiere et al., 2013), the role of CS and its cortical inputs in the selection of spontaneous behaviors has not been explored. We therefore studied the role of CS corticostriatal circuits in behavioral selection in an open field context.Surprisingly, using fiber photometry in this unconstrained environment, we found that population calcium activity in CS was specifically increased at onset of grooming, and not at onset of other spontaneous behaviors such as rearing or locomotion. Supporting a potential selective role for CS in the initiation of grooming, bilateral optogenetic stimulation of CS evoked immediate onset grooming-related movements. However, these movements resembled subcomponents of grooming behavior and not full-fledged grooming bouts, suggesting that additional input(s) are required to appropriately sequence and sustain this complex motor behavior once initiated. Consistent with this idea, optogenetic stimulation of CS inputs from ALM generated sustained grooming responses that evolved on a time-course paralleling CS activation monitored using single-cell calcium imaging. Furthermore, fiber photometry in ALM demonstrated a gradual ramp in calcium activity that peaked at time of grooming termination, supporting a potential role for ALM in encoding length of this spontaneous sequenced behavior. Finally, dual color dual region fiber photometry indicated that CS activation precedes ALM during naturalistic grooming sequences. Taken together, these data support a novel model in which CS activity is sufficient to initiate grooming behavior, but ALM activity is necessary to sustain and encode the length of grooming bouts. Thus, the use of an unconstrained behavioral paradigm has allowed us to uncover surprising roles for CS and ALM in the initiation and maintenance of spontaneous sequenced behaviors.

scholarly journals Cholinergic upregulation by optogenetic stimulation of nucleus basalis after photothrombotic stroke in forelimb somatosensory cortex improves endpoint and motor but not sensory control of skilled reaching in mice

2020 ◽  
Author(s):  
Behroo Mirza Agha ◽  
Roya Akbary ◽  
Arashk Ghasroddashti ◽  
Mojtaba Nazari-Ahangarkolaee ◽  
Ian Q. Whishaw ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Sensorimotor Integration ◽  
Motor Behavior ◽  
Field Potential ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Optogenetic Stimulation ◽  
Photothrombotic Stroke ◽  
Skilled Reaching ◽  
Stimulation Of

AbstractA network of cholinergic neurons in the basal forebrain innerve the forebrain and are proposed to contribute to a variety of functions including attention, and cortical plasticity. This study examined the contribution of the nucleus basalis cholinergic projection to the sensorimotor cortex on recovery on a skilled reach-to-eat task following photothrombotic stroke in the forelimb region of the somatosensory cortex. Mice were trained to perform a single-pellet skilled reaching task and their pre and poststroke performance, from Day 4 to Day 28 poststroke, was assessed frame-by-frame by video analysis with end point, movement and sensorimotor integration measures. Somatosensory forelimb lesions produced impairments in endpoint and movement component measures of reaching and increased the incidence of fictive eating, a sensory impairment in mistaking a missed reach for a successful reach. Upregulated acetylcholine (ACh) release, as measured by local field potential recording, elicited via optogenetic stimulation of the nucleus basalis improved recovery of reaching and improved movement scores but did not affect a sensorimotor integration impairment poststroke. The results show that the mouse cortical forelimb somatosensory region contributes to forelimb motor behavior and suggest that ACh upregulation could serve as an adjunct to behavioral therapy for the acute treatment of stroke.

scholarly journals 0074 Inhibitory Neurons in the Dorsomedial Medulla Promote REM Sleep

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A30-A30
Author(s):  
J Stucynski ◽  
A Schott ◽  
J Baik ◽  
J Hong ◽  
F Weber ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Inhibitory Neurons ◽  
Brain State ◽  
Sleep Regulation ◽  
Optogenetic Stimulation ◽  
Electrophysiological Recordings ◽  
Stimulation Of

Abstract Introduction The neural circuits controlling rapid eye movement (REM) sleep, and in particular the role of the medulla in regulating this brain state, remains an active area of study. Previous electrophysiological recordings in the dorsomedial medulla (DM) and electrical stimulation experiments suggested an important role of this area in the control of REM sleep. However the identity of the involved neurons and their precise role in REM sleep regulation are still unclear. Methods The properties of DM GAD2 neurons in mice were investigated through stereotaxic injection of CRE-dependent viruses in conjunction with implantation of electrodes for electroencephalogram (EEG) and electromyogram (EMG) recordings and optic fibers. Experiments included in vivo calcium imaging (fiber photometry) across sleep and wake states, optogenetic stimulation of cell bodies, chemogenetic excitation and suppression (DREADDs), and connectivity mapping using viral tracing and optogenetics. Results Imaging the calcium activity of DM GAD2 neurons in vivo indicates that these neurons are most active during REM sleep. Optogenetic stimulation of DM GAD2 neurons reliably triggered transitions into REM sleep from NREM sleep. Consistent with this, chemogenetic activation of DM GAD2 neurons increased the amount of REM sleep while inhibition suppressed its occurrence and enhanced NREM sleep. Anatomical tracing revealed that DM GAD2 neurons project to several areas involved in sleep / wake regulation including the wake-promoting locus coeruleus (LC) and the REM sleep-suppressing ventrolateral periaquaductal gray (vlPAG). Optogenetic activation of axonal projections from DM to LC, and DM to vlPAG was sufficient to induce REM sleep. Conclusion These experiments demonstrate that DM inhibitory neurons expressing GAD2 powerfully promote initiation of REM sleep in mice. These findings further characterize the dorsomedial medulla as a critical structure involved in REM sleep regulation and inform future investigations of the REM sleep circuitry. Support R01 HL149133

scholarly journals Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

2020 ◽  
Author(s):  
Ya-Dong Li ◽  
Yan-Jia Luo ◽  
Wei Xu ◽  
Jing Ge ◽  
Yoan Cherasse ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Gabaergic Neurons ◽  
Population Activity ◽  
Lateral Habenula ◽  
Optogenetic Stimulation ◽  
Ventral Tegmental ◽  
Stimulation Of

Abstract The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.

scholarly journals The role of the right presupplementary motor area in stopping action: two studies with event-related transcranial magnetic stimulation

2012 ◽  
Vol 108 (2) ◽  
pp. 380-389 ◽  
Author(s):  
Weidong Cai ◽  
Jobi S. George ◽  
Frederick Verbruggen ◽  
Christopher D. Chambers ◽  
Adam R. Aron
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Inferior Frontal Gyrus ◽  
Stop Signal ◽  
Motor Area ◽  
Stopping Rules ◽  
Stop Signal Task ◽  
The Right ◽  
Stimulation Of

Rapidly stopping action engages a network in the brain including the right presupplementary motor area (preSMA), the right inferior frontal gyrus, and the basal ganglia. Yet the functional role of these different regions within the overall network still remains unclear. Here we focused on the role of the right preSMA in behavioral stopping. We hypothesized that the underlying neurocognitive function of this region is one or more of setting up a stopping rule in advance, modulating response tendencies (e.g., slowing down in anticipation of stopping), and implementing stopping when the stop signal occurs. We performed two experiments with magnetic resonance imaging (MRI)–guided, event-related, transcranial magnetic stimulation(TMS), during the performance of variants of the stop signal task. In experiment 1 we show that stimulation of the right preSMA versus vertex (control site) slowed the implementation of stopping (measured via stop signal reaction time) but had no influence on modulation of response tendencies. In experiment 2, we showed that stimulation of the right preSMA slowed implementation of stopping in a mechanistically selective form of stopping but had no influence on setting up stopping rules. The results go beyond the replication of prior findings by showing that TMS of the right preSMA impairs stopping behavior (including a behaviorally selective form of stopping) through a specific disruption of the implementation of stopping. Future studies are required to establish whether this was due to stimulation of the right preSMA itself or because of remote effects on the wider stopping network.

Gaze-Stabilizing Deficits and Latent Nystagmus in Monkeys With Early-Onset Visual Deprivation: Role of the Pretectal NOT

2001 ◽  
Vol 86 (2) ◽  
pp. 662-675 ◽  
Author(s):  
Michael J. Mustari ◽  
Ronald J. Tusa ◽  
Andrew F. Burrows ◽  
Albert F. Fuchs ◽  
Christine A. Livingston
Keyword(s):  
Electrical Stimulation ◽  
Visual Motion ◽  
Motor Behavior ◽  
Optic Tract ◽  
Wide Range ◽  
Latent Nystagmus ◽  
Contralateral Eye ◽  
The Right ◽  
Stimulation Of

We studied the role of the pretectal nucleus of the optic tract (NOT) in the development of monocular optokinetic nystagmus (OKN) asymmetries and latent nystagmus (LN) in two monkeys reared with binocular deprivation (BD) caused by binocular eyelid suture for either the first 25 or 55 days of life. Single-unit recordings were performed in the right and left NOT of both monkeys at 2–3 yr of age and compared with similar unit recordings in normally reared monkeys. We also examined ocular motor behavior during electrical stimulation of the NOT and during pharmacological inactivation and activation using GABAA agonists and antagonists. In BD animals a large proportion of NOT units was dominated by the contralateral eye, in striking contrast to normal animals where 100% of NOT units were sensitive to stimuli delivered to either eye. In the 55-day BD animal no binocularly sensitive neurons were found, while in the 25-day BD animal 60% of NOT units retained at least some binocular sensitivity. Differences in direction sensitivity were also observed in BD animals. We found that 56% of units in the 55-day BD monkey and 10% of units in the 25-day BD monkey responded preferentially to contraversive visual motion. In contrast, only 5% of the NOT units encountered in normally reared monkeys respond preferentially during contraversive visual motion, the rest were most sensitive to ipsiversive visual motion. NOT neurons of BD monkeys showed a wide range of speed sensitivities similar to that of normal monkeys. Unilateral electrical stimulation of the NOT in BD animals induced a conjugate nystagmus with slow phases directed toward the side of stimulation. When we blocked the activity of NOT units with muscimol, a potent GABAA agonist, LN was abolished. In contrast, LN was increased when spontaneous activity of the NOT was enhanced with bicuculline, a GABAA antagonist. Our results indicate that the NOT in BD monkeys plays an important role in the OKN deficits and LN generation during monocular viewing. We hypothesize that the large proportion of units dominated by the contralateral eye contribute to the development of monocular OKN asymmetries and LN.

scholarly journals Cholinergic upregulation by optogenetic stimulation of nucleus basalis after photothrombotic stroke in forelimb somatosensory cortex improves endpoint and motor but not sensory control of skilled reaching in mice

2020 ◽  
pp. 0271678X2096893
Author(s):  
Behroo Mirza Agha ◽  
Roya Akbary ◽  
Arashk Ghasroddashti ◽  
Mojtaba Nazari-Ahangarkolaee ◽  
Ian Q Whishaw ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Sensorimotor Integration ◽  
Motor Behavior ◽  
Field Potential ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Optogenetic Stimulation ◽  
Photothrombotic Stroke ◽  
Skilled Reaching ◽  
Stimulation Of

A network of cholinergic neurons in the basal forebrain innerve the forebrain and are proposed to contribute to a variety of functions including cortical plasticity, attention, and sensorimotor behavior. This study examined the contribution of the nucleus basalis cholinergic projection to the sensorimotor cortex on recovery on a skilled reach-to-eat task following photothrombotic stroke in the forelimb region of the somatosensory cortex. Mice were trained to perform a single pellet skilled reaching task and their pre and poststroke performance, from Day 4 to Day 28 poststroke, was assessed frame-by-frame by video analysis with endpoint, movement and sensorimotor integration measures. Somatosensory forelimb lesions produced impairments in endpoint and movement component measures of reaching and increased the incidence of fictive eating, a sensory impairment in mistaking a missed reach for a successful reach. Upregulated acetylcholine (ACh) release, as measured by local field potential recording, elicited via optogenetic stimulation of the nucleus basalis improved recovery of reaching and improved movement scores but did not affect sensorimotor integration impairment poststroke. The results show that the mouse cortical forelimb somatosensory region contributes to forelimb motor behavior and suggest that ACh upregulation could serve as an adjunct to behavioral therapy for acute treatment of stroke.

scholarly journals 0154 Role of Noradrenergic Projection to the Preoptic Area in Regulation of Arousal

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A61-A61
Author(s):  
H Antila ◽  
I Kwak ◽  
I Covarrubias ◽  
J Baik ◽  
J Hong ◽  
...  
Keyword(s):  
Preoptic Area ◽  
Brain Regions ◽  
Brain State ◽  
Research Fellowship ◽  
Optogenetic Stimulation ◽  
Long Time ◽  
Brain States ◽  
Stimulation Of

Abstract Introduction Locus coeruleus (LC) is a noradrenergic nucleus in the brainstem involved in the regulation of attention, arousal, mood and sensory gating. LC projects to multiple brain regions and recent development of novel systems neuroscience tools allows the dissection of projection-specific LC function in more detail. One of the regions with noradrenergic projection is the preoptic area of the hypothalamus (POA). POA has been shown to contain neurons that are important for regulating sleep, and we have examined the function of the LC projection to the POA in sleep and arousal. Methods We used optogenetics, chemogenetics, fiber photometry and in vivo electrophysiology to study the function of LC noradrenergic projection to the POA. Results Norepinephrine release in the POA fluctuates with brain state changes indicating that the LC to POA projection may be involved in regulating sleep and arousal. Optogenetic stimulation of LC fibers in the POA promotes wakefulness. Furthermore, optogenetic stimulation of the LC fibers in the POA modulates the activity of sleep- and wake-active neurons. Conclusion We have identified the role of the LC noradrenergic projection to the POA in the regulation of brain states. Stimulation of the LC fibers in the POA promotes wakefulness and modulates the activity dynamics of sleep- and wake-active neurons in the POA. Our results provide more detailed information about the role of this specific projection, which has been known to exist for a long time, but with insufficient in vivo evidence of its precise function. Support Sigrid Juselius foundation, Alfred P. Sloan Research Fellowship in Neuroscience, The Whitehall foundation grant, McCabe Fund Award, NARSAD Young Investigator Award.

scholarly journals Predictive encoding of motor behavior in the supplementary motor area is disrupted in parkinsonism

2018 ◽  
Vol 120 (3) ◽  
pp. 1247-1255 ◽  
Author(s):  
Claudia M. Hendrix ◽  
Brett A. Campbell ◽  
Benjamin J. Tittle ◽  
Luke A. Johnson ◽  
Kenneth B. Baker ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Motor Behavior ◽  
Activity Patterns ◽  
Movement Planning ◽  
Motor Area ◽  
Beta Band ◽  
Reaching Task ◽  
Cortical Areas ◽  
Trial Basis

Many studies suggest that Parkinson’s disease (PD) is associated with changes in neuronal activity patterns throughout the basal ganglia-thalamocortical motor circuit. There are limited electrophysiological data, however, describing how parkinsonism impacts the presupplementary motor area (pre-SMA) and SMA proper (SMAp), cortical areas known to be involved in movement planning and motor control. In this study, local field potentials (LFPs) were recorded in the pre-SMA/SMAp of a nonhuman primate during a visually cued reaching task. Recordings were made in the same subject in both the naive and parkinsonian state using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism. We found that in the naive animal, well before a go-cue providing instruction of reach onset and direction was given, LFP activity was dynamically modulated in both high (20–30 Hz) and low beta (10–20 Hz) bands, and the magnitude of this modulation (e.g., decrease/increase in beta amplitude for each band, respectively) correlated linearly with reaction time (RT) on a trial-to-trial basis, suggesting it may predictively encode for RT. Consistent with this hypothesis, we observed that this activity was more prominent within the pre-SMA compared with SMAp. In the parkinsonian state, however, pre-SMA/SMAp beta band modulation was disrupted, particularly in the high beta band, such that the predictive encoding of RT was significantly diminished. In addition, the predictive encoding of RT preferentially within pre-SMA over SMAp was lost. These findings add to our understanding of the role of pre-SMA/SMAp in motor behavior and suggest a fundamental role of these cortical areas in early preparatory and premovement processes that are altered in parkinsonism. NEW & NOTEWORTHY Goal-directed movements, such as reaching for an object, necessitate temporal preparation and organization of information processing within the basal ganglia-thalamocortical motor network. Impaired movement in parkinsonism is thought to be the result of pathophysiological activity disrupting information flow within this network. This work provides neurophysiological evidence linking altered motor preplanning processes encoded in pre-SMA/SMAp beta band modulation to the pathogenesis of motor disturbances in parkinsonism.

scholarly journals Selective Optogenetic Stimulation of Glutamatergic, but not GABAergic, Vestibular Nuclei Neurons Induces Immediate and Reversible Postural Imbalance in Mice

2020 ◽  
Author(s):  
Q. Montardy ◽  
M. Wei ◽  
T. Yi ◽  
X. Liu ◽  
Z. Zhou ◽  
...  
Keyword(s):  
Vestibular Nuclei ◽  
Gabaergic Neurons ◽  
Support Surface ◽  
List Type ◽  
Optogenetic Stimulation ◽  
Short Period ◽  
Locomotor Deficits ◽  
Locomotor Behaviors ◽  
Stimulation Of

AbstractGlutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate that glutamatergic, but not GABAergic VN neuronal subpopulation is responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface dramatically increased in VNVGluT2+ mice, and rapidly fell back to baseline after stimulation, whilst it remained unchanged during similar stimulation of VNGAD2+ mice. This effect persisted when vestibular compensation was removed. Posturo-locomotor alterations evoked in VNVGluT2+ animals were still present immediately after stimulation, while they disappeared 1h later. Overall, these results indicate a fundamental role for VNVGluT2+ neurons in balance and posturo-locomotor functions, but not for VNGAD2+ neurons, in this specific context. This new optogenetic approach will be useful to characterize the role of the different VN neuronal populations involved in vestibular physiology and pathophysiology.HighlightsFor the first time, Vestibular nuclei were optogenetically stimulated in free-moving animals, to asses for glutamatergic and GABAergic neurons functions in posturo-locomotor behaviors.Brief optogenetic activation of VNVGluT2+, but not VNGAD2+, induced immediate and strong postural deficit.Stimulation of VNVGluT2+ neurons provoked an imbalance with continuous effect on locomotion for a short period of time after stimulation.These results are comparable to the classical vestibular deafferentation models during their peak of deficit, and set optogenetic stimulation as a new model to study vestibular deficits.

scholarly journals Optogenetic Dissection of Neural Circuits Underlying Stress-Induced Mood Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Liu ◽  
Zhinuo Zhang ◽  
Wenjuan Zhang
Keyword(s):  
Mood Disorders ◽  
Stress Reactivity ◽  
Neural Circuits ◽  
Web Of Science ◽  
Anxiety And Depression ◽  
Social Avoidance ◽  
Optogenetic Stimulation ◽  
Induced Mood ◽  
Stimulation Of

Objectives: This review aims to (i) summarize the literature on optogenetic applications of different stress-induced mood disorder models of the medial prefrontal cortex (mPFC) and its projection circuits, and (ii) examine methodological variability across the literature and how such variations may influence the underlying circuits of stress-induced mood disorders.Methods: A variety of databases (PubMed, Web of Science, Elsevier, Springer, and Wiley) were systematically searched to identify optogenetic studies that applied to mood disorders in the context of stress.Results: Eleven studies on optogenetic stimulation of the mPFC and the effect of its efferent circuitry on anxiety- and depression-like behaviors in different rodent models were selected. The results showed that the optogenetics (i) can provide insights into the underlying circuits of mood disorders in the context of stress (ii) and also points out new therapeutic strategies for treating mood disorders.Conclusions: These findings indicate a clear role for the mPFC in social avoidance, and highlight the central role of stress reactivity circuitry that may be targeted for the treatment of stress-induced mood disorders.

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