scholarly journals Opposing Influence of Sensory and Motor Cortical Input on Striatal Circuitry and Choice Behavior

2018 ◽  
Author(s):  
Christian R. Lee ◽  
Alex J. Yonk ◽  
Joost Wiskerke ◽  
Kenneth G. Paradiso ◽  
James M. Tepper ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Dorsal Striatum ◽  
Behavioral Effect ◽  
Projection Neurons ◽  
Cortical Input ◽  
Optogenetic Stimulation ◽  
Main Input ◽  
Opposing Effects ◽  
Stimulation Of

SummaryThe striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1- or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV interneurons. Optogenetic stimulation of M1 afferents produced the opposite behavioral effect. Thus, our results suggest opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry.

scholarly journals Dysregulation of the basal ganglia indirect pathway prior to cell loss in the Q175 mouse model of Huntington's disease

2021 ◽  
Author(s):  
Joshua Callahan ◽  
David L Wokosin ◽  
Mark D Bevan
Keyword(s):  
Basal Ganglia ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Ex Vivo ◽  
Cell Loss ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Cortical Input ◽  
Psychomotor Symptoms

The psychomotor symptoms of Huntington's disease (HD) are linked to degeneration of the basal ganglia indirect pathway. To determine how this pathway is perturbed prior to cell loss, optogenetic- and reporter-guided electrophysiological interrogation approaches were applied to early symptomatic 6-month-old Q175 HD mice. Although cortical activity was unaffected, indirect pathway striatal projection neurons were hypoactive in vivo, consistent with reduced cortical input strength and dendritic excitability. Downstream parvalbumin-expressing prototypic external globus pallidus (GPe) neurons were hyperactive in vivo and exhibited elevated autonomous firing ex vivo. Optogenetic inhibition of prototypic GPe neurons ameliorated the abnormal hypoactivity of postsynaptic subthalamic nucleus (STN) and putative arkypallidal neurons in vivo. In contrast to STN neurons, autonomous arkypallidal activity was unimpaired ex vivo. Together with previous studies, these findings demonstrate that basal ganglia indirect pathway neurons are highly dysregulated in Q175 mice through changes in presynaptic activity and/or intrinsic properties 6-12 months before cell loss.

scholarly journals Optogenetic stimulation of medial amygdala GABA neurons with kinetically different channelrhodopsin variants yield opposite behavioral outcomes

2021 ◽  
Author(s):  
Aiste Baleisyte ◽  
Ralf Schneggenburger ◽  
Olexiy Kochubey
Keyword(s):  
Behavioral Outcomes ◽  
Inhibitory Neurons ◽  
Projection Neurons ◽  
Medial Amygdala ◽  
Optogenetic Stimulation ◽  
Gaba Neurons ◽  
Local Inhibition ◽  
Neuron Populations ◽  
Stimulation Of

Optogenetic manipulation of genetically-specified neuron populations has become a key tool in circuit neuroscience. The medial amygdala (MeA) receives pheromone information about conspecifics and has crucial functions in social behaviors; interestingly, this amygdalar structure contains a majority of GABAergic projection neurons. A previous study showed that optogenetic activation of MeA GABA neurons with channelrhodopsin-2H134R (ChR2) strongly enhanced inter-male aggression (Hong et al. 2014, Cell). When we attempted to reproduce these findings, accidentally using a faster channelrhodopsin variant (channelrhodopsin-2H134R,E123T or ChETA), we found the opposite results. We therefore systematically compared the behavioral outcome of optogenetic stimulation of MeApd GABA neurons with ChETA versus ChR2, employing two widely used AAV serotypes. This revealed that optogenetic stimulation with ChETA suppressed aggression, whereas optogenetic stimulation with ChR2 increased aggression. Recordings of membrane potential changes following optogenetic stimulation with ChETA versus ChR2 revealed larger plateau depolarizations, smaller action potential amplitudes, and larger local inhibition of neighboring inhibitory neurons with ChR2 as compared to ChETA. Our study shows that channelrhodopsin variants have to be chosen with care for in-vivo optogenetic experiments. Furthermore, the role of MeApd GABA neurons in aggression control should be re-evaluated.

scholarly journals Wireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal models

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Philipp Gutruf ◽  
Rose T. Yin ◽  
K. Benjamin Lee ◽  
Jokubas Ausra ◽  
Jaclyn A. Brennan ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Small Animal ◽  
In Vivo Studies ◽  
Cardiovascular Research ◽  
Optogenetic Stimulation ◽  
Wide Range ◽  
Small Animal Models ◽  
Wireless Energy Harvesting ◽  
Stimulation Of

AbstractSmall animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology.

scholarly journals Amygdala-cortical control of striatal plasticity drives the acquisition of goal-directed action

2020 ◽  
Author(s):  
Simon D. Fisher ◽  
Lachlan A. Ferguson ◽  
Jesus Bertran-Gonzalez ◽  
Bernard W. Balleine
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Projection Neurons ◽  
Cortical Control ◽  
Indirect Pathway ◽  
Optogenetic Stimulation ◽  
Directed Action ◽  
Directed Learning ◽  
Corticostriatal Plasticity ◽  
Stimulation Of

SummaryThe acquisition of goal-directed action requires the encoding of specific action-outcome associations involving plasticity in the posterior dorsomedial striatum (pDMS). We first investigated the relative involvement of the major inputs to the pDMS argued to be involved in this learning-related plasticity, from prelimbic prefrontal cortex (PL) and from the basolateral amygdala (BLA). Using ex vivo optogenetic stimulation of PL or BLA terminals in pDMS, we found that goal-directed learning potentiated the PL input to direct pathway spiny projection neurons (dSPNs) bilaterally but not to indirect pathway neurons (iSPNs). In contrast, learning-related plasticity was not observed in the direct BLA-pDMS pathway. Using toxicogenetics, we ablated BLA projections to either pDMS or PL and found that only the latter was necessary for goal-directed learning. Importantly, transient inactivation of the BLA during goal-directed learning prevented the PL-pDMS potentiation of dSPNs, establishing that the BLA input to the PL is necessary for the corticostriatal plasticity underlying goal-directed learning.

scholarly journals Optogenetic stimulation of VIPergic SCN neurons induces photoperiodic changes in the mammalian circadian clock

2021 ◽  
Author(s):  
Michael C. Tackenberg ◽  
Jacob J. Hughey ◽  
Douglas G. McMahon
Keyword(s):  
Ex Vivo ◽  
Day Length ◽  
Optogenetic Stimulation ◽  
Period 2 ◽  
Free Running ◽  
Free Running Period ◽  
The Brain ◽  
Long Photoperiod ◽  
Stimulation Of

SummaryCircadian clocks play key roles in how organisms respond to and even anticipate seasonal change in day length, or photoperiod. In mammals, photoperiod is encoded by the central circadian pacemaker in the brain, the suprachiasmatic nucleus (SCN). The subpopulation of SCN neurons that secrete the neuropeptide VIP mediate the transmission of light information within the SCN neural network, suggesting a role for these neurons in circadian plasticity in response to light information that has yet to be directly tested. Here, we used in vivo optogenetic stimulation of VIPergic SCN neurons followed by ex vivo PERIOD 2::LUCIFERASE (PER2::LUC) bioluminescent imaging to test whether activation of this SCN neuron sub-population can induce SCN network changes that are hallmarks of photoperiodic encoding. We found that optogenetic stimulation designed to mimic a long photoperiod indeed altered subsequent SCN entrained phase, increased the phase dispersal of PER2 rhythms within the SCN network, and shortened SCN free-running period – similar to the effects of a true extension of photoperiod. Optogenetic stimulation also induced analogous changes on related aspects of locomotor behavior in vivo. Thus, selective activation of VIPergic SCN neurons induces photoperiodic network plasticity in the SCN which underpins photoperiodic entrainment of behavior.

scholarly journals In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transduction

2021 ◽  
Author(s):  
Antoine Chaffiol ◽  
Matthieu Provansal ◽  
Corentin Joffrois ◽  
Kévin Blaize ◽  
Guillaume Labernede ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Information Transfer ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Spatiotemporal Resolution ◽  
Fluorescent Reporter ◽  
Optogenetic Stimulation ◽  
Stimulation Of

SummaryVarious therapeutic strategies for vision restoration have been developed, including retinal prostheses [1–4], stem cell transplantation [5–8] and optogenetic therapies [9,10,19,11–18]. In optogenetic therapy, the residual retinal neurons surviving the pathological degenerative process are rendered light-sensitive. Using this approach, we targeted the retinal ganglion cells (RGCs) through the in vivo expression of an ectopic light-sensitive ion channel, ChrimsonR [13] coupled to the fluorescent reporter tdTomato. The application of this strategy to blind patients [20] suffering from retinal dystrophies raises important concerns about the long-term functional expression of efficient signal transmission to higher brain centers (i.e. the visual cortex). We have previously shown that the transduced retina displays high spatiotemporal resolution ex vivo, compatible with the perception of highly dynamic visual scenes at light levels suitable for use in humans. Other studies have provided evidence of retinal activation in vivo [17]. Here, we demonstrate, in non-human primates, sustained functional efficacy ~20 months after delivery of an AAV2.7m8-ChrimsonR-tdTomato vector similar to that currently undergoing clinical evaluation. Our results reveal a persistence of expression in the perifovea, mediating information transfer to higher brain centers. Indeed, we recorded visually evoked potentials in the primary visual cortex of anesthetized animals in response to optogenetic retinal activation. We used an intravitreal injection of synaptic blockers to isolate the cortical component resulting from the in vivo optogenetic stimulation of primate RGCs. Our findings demonstrate the long-term functional efficacy of optogenetic retinal information transfer to the brain in vivo.

scholarly journals Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

2020 ◽  
Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Dorsal Striatum ◽  
Reaction Time Task ◽  
Emission Computed Tomography ◽  
Novelty Preference ◽  
Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

scholarly journals Enhanced food motivation in obese mice is controlled by D1R expressing spiny projection neurons in the nucleus accumbens.

2022 ◽  
Author(s):  
Bridget A Matikainen-Ankney ◽  
Alex A Legaria ◽  
Yvan M Vachez ◽  
Caitlin A Murphy ◽  
Yiyan A Pan ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Food Reward ◽  
Ex Vivo ◽  
D1 Receptor ◽  
Physical Work ◽  
Projection Neurons ◽  
Food Motivation ◽  
Obese Mice ◽  
Food Seeking

Obesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. In addition to homeostatic feeding mechanisms, there is growing recognition of the involvement of food reward and motivation in the development of obesity. However, it remains unclear how brain circuits that control food reward and motivation are altered in obese animals. Here, we tested the hypothesis that signaling through pro-motivational circuits in the core of the nucleus accumbens (NAc) is enhanced in the obese state, leading to invigoration of food seeking. Using a novel behavioral assay that quantifies physical work during food seeking, we confirmed that obese mice work harder than lean mice to obtain food, consistent with an increase in the relative reinforcing value of food in the obese state. To explain this behavioral finding, we recorded neural activity in the NAc core with both in vivo electrophysiology and cell-type specific calcium fiber photometry. Here we observed greater activation of D1-receptor expressing NAc spiny projection neurons (NAc D1SPNs) during food seeking in obese mice relative to lean mice. With ex vivo slice physiology we identified both pre- and post-synaptic mechanisms that contribute to this enhancement in NAc D1SPN activity in obese mice. Finally, blocking synaptic transmission from D1SPNs decreased physical work during food seeking and attenuated high-fat diet-induced weight gain. These experiments demonstrate that obesity is associated with a selective increase in the activity of D1SPNs during food seeking, which enhances the vigor of food seeking. This work also establishes the necessity of D1SPNs in the development of diet-induced obesity, identifying a novel potential therapeutic target.

scholarly journals Parylene photonics: a flexible, broadband optical waveguide platform with integrated micromirrors for biointerfaces

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jay W. Reddy ◽  
Maya Lassiter ◽  
Maysamreza Chamanzar
Keyword(s):  
Optical Waveguides ◽  
Brain Activity ◽  
Low Loss ◽  
Parylene C ◽  
Optogenetic Stimulation ◽  
Patterned Illumination ◽  
The Brain ◽  
532 Nm ◽  
Stimulation Of

Abstract Targeted light delivery into biological tissue is needed in applications such as optogenetic stimulation of the brain and in vivo functional or structural imaging of tissue. These applications require very compact, soft, and flexible implants that minimize damage to the tissue. Here, we demonstrate a novel implantable photonic platform based on a high-density, flexible array of ultracompact (30 μm × 5 μm), low-loss (3.2 dB/cm at λ = 680 nm, 4.1 dB/cm at λ = 633 nm, 4.9 dB/cm at λ = 532 nm, 6.1 dB/cm at λ = 450 nm) optical waveguides composed of biocompatible polymers Parylene C and polydimethylsiloxane (PDMS). This photonic platform features unique embedded input/output micromirrors that redirect light from the waveguides perpendicularly to the surface of the array for localized, patterned illumination in tissue. This architecture enables the design of a fully flexible, compact integrated photonic system for applications such as in vivo chronic optogenetic stimulation of brain activity.

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

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