scholarly journals Causal role for the subthalamic nucleus in interrupting behavior

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Kathryn H Fife ◽  
Navarre A Gutierrez-Reed ◽  
Vivien Zell ◽  
Julie Bailly ◽  
Christina M Lewis ◽  
...  
Keyword(s):  
Subthalamic Nucleus ◽  
Behavioral Response ◽  
Causal Role ◽  
Projection Neurons ◽  
Response Suppression ◽  
Disruptive Effect ◽  
Optogenetic Stimulation ◽  
Conflicting Information ◽  
Necessary And Sufficient ◽  
Stimulation Of

Stopping or pausing in response to threats, conflicting information, or surprise is fundamental to behavior. Evidence across species has shown that the subthalamic nucleus (STN) is activated by scenarios involving stopping or pausing, yet evidence that the STN causally implements stops or pauses is lacking. Here we used optogenetics to activate or inhibit mouse STN to test its putative causal role. We first demonstrated that optogenetic stimulation of the STN excited its major projection targets. Next we showed that brief activation of STN projection neurons was sufficient to interrupt or pause a self-initiated bout of licking. Finally, we developed an assay in which surprise was used to interrupt licking, and showed that STN inhibition reduced the disruptive effect of surprise. Thus STN activation interrupts behavior, and blocking the STN blunts the interruptive effect of surprise. These results provide strong evidence that the STN is both necessary and sufficient for such forms of behavioral response suppression.

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 Optogenetic Stimulation of Lateral Orbitofronto-Striatal Pathway Suppresses Compulsive Behaviors

Science ◽  
2013 ◽  
Vol 340 (6137) ◽  
pp. 1243-1246 ◽  
Author(s):  
Eric Burguière ◽  
Patrícia Monteiro ◽  
Guoping Feng ◽  
Ann M. Graybiel
Keyword(s):  
Response Inhibition ◽  
Behavioral Response ◽  
Repetitive Behavior ◽  
Projection Neuron ◽  
Repetitive Behaviors ◽  
Neuron Activity ◽  
Down Regulation ◽  
Delay Conditioning ◽  
Optogenetic Stimulation ◽  
Stimulation Of

Dysfunctions in frontostriatal brain circuits have been implicated in neuropsychiatric disorders, including those characterized by the presence of repetitive behaviors. We developed an optogenetic approach to block repetitive, compulsive behavior in a mouse model in which deletion of the synaptic scaffolding gene, Sapap3, results in excessive grooming. With a delay-conditioning task, we identified in the mutants a selective deficit in behavioral response inhibition and found this to be associated with defective down-regulation of striatal projection neuron activity. Focused optogenetic stimulation of the lateral orbitofrontal cortex and its terminals in the striatum restored the behavioral response inhibition, restored the defective down-regulation, and compensated for impaired fast-spiking neuron striatal microcircuits. These findings raise promising potential for the design of targeted therapy for disorders involving excessive repetitive behavior.

scholarly journals Aversion encoded in the subthalamic nucleus

2020 ◽  
Author(s):  
Gian Pietro Serra ◽  
Adriane Guillaumin ◽  
Jérome Baufreton ◽  
François Georges ◽  
Åsa Wallén-Mackenzie
Keyword(s):  
Basal Ganglia ◽  
Subthalamic Nucleus ◽  
Place Preference ◽  
Ventral Pallidum ◽  
Lateral Habenula ◽  
Place Aversion ◽  
Optogenetic Stimulation ◽  
Ongoing Behavior ◽  
Aversive Behavior ◽  
Stimulation Of

AbstractActivation of the subthalamic nucleus (STN) is associated with the stopping of ongoing behavior via the basal ganglia. However, we recently observed that optogenetic STN excitation induced a strong jumping/escaping behavior. We hypothesized that STN activation is aversive. To test this, place preference was assessed. Optogenetic excitation of the STN caused potent place aversion. Causality between STN activation and aversion has not been demonstrated previously. The lateral habenula (LHb) is a critical hub for aversion. Optogenetic stimulation of the STN indeed caused firing of LHb neurons, but with delay, suggesting the involvement of a polysynaptic circuit. To unravel a putative pathway, the ventral pallidum (VP) was investigated. VP receives projections from the STN and in turn projects to the LHb. Optogenetic excitation of STN-VP terminals caused firing of VP neurons and induced aversive behavior. This study identifies the STN as critical hub for aversion, potentially mediated via an STN-VP-LHb pathway.

scholarly journals Localized Synaptic Potentiation is Necessary and Sufficient for Context Fear Memory

2022 ◽  
Author(s):  
Leonardo M Cardozo ◽  
Blythe C Dillingham ◽  
Andre F Sousa ◽  
Westley Dang ◽  
Nicholas Job ◽  
...  
Keyword(s):  
High Frequency ◽  
Basolateral Amygdala ◽  
Fear Learning ◽  
Excitatory Synapses ◽  
Synaptic Potentiation ◽  
Optogenetic Stimulation ◽  
Impaired Memory ◽  
Synaptic Changes ◽  
Necessary And Sufficient ◽  
Stimulation Of

The nature and distribution of the synaptic changes that underlie memory are not well understood. We examined the synaptic plasticity behind context fear learning and found that conditioning produced potentiation of excitatory synapses specifically onto the basolateral amygdala neurons activated during learning. This synaptic potentiation lasted at least 7 days, and its disruption impaired memory recall. High frequency optogenetic stimulation of the CS and US-activated ensembles or biochemical induction of synaptic potentiation in US-responsive neurons alone was sufficient to produce a context fear association without prior associative training. These results suggest that plasticity of CS inputs onto US-responsive amygdala neurons is a necessary and sufficient step in forming context fear associations, and that context discrimination is determined by the CS-specific amygdala inputs activated during retrieval.

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 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.

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