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 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 Striatal direct and indirect pathway neurons differentially control the encoding and updating of goal-directed learning

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
James Peak ◽  
Billy Chieng ◽  
Genevra Hart ◽  
Bernard W Balleine
Keyword(s):  
Response Bias ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Response Flexibility ◽  
Directed Action ◽  
Elevated Expression ◽  
Directed Learning ◽  
Series Of Experiments ◽  
Dorsomedial Striatum

The posterior dorsomedial striatum (pDMS) is necessary for goal-directed action; however, the role of the direct (dSPN) and indirect (iSPN) spiny projection neurons in the pDMS in such actions remains unclear. In this series of experiments, we examined the role of pDMS SPNs in goal-directed action in rats and found that whereas dSPNs were critical for goal-directed learning and for energizing the learned response, iSPNs were involved in updating that learning to support response flexibility. Instrumental training elevated expression of the plasticity marker Zif268 in dSPNs only, and chemogenetic suppression of dSPN activity during training prevented goal-directed learning. Unilateral optogenetic inhibition of dSPNs induced an ipsilateral response bias in goal-directed action performance. In contrast, although initial goal-directed learning was unaffected by iSPN manipulations, optogenetic inhibition of iSPNs, but not dSPNs, impaired the updating of this learning and attenuated response flexibility after changes in the action-outcome contingency.

scholarly journals Striatal direct and indirect pathway neurons differentially control the encoding and updating of goal-directed learning

2020 ◽  
Author(s):  
James Peak ◽  
Billy Chieng ◽  
Genevra Hart ◽  
Bernard W. Balleine
Keyword(s):  
Response Bias ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Response Flexibility ◽  
Directed Action ◽  
Elevated Expression ◽  
Directed Learning ◽  
Series Of Experiments ◽  
Dorsomedial Striatum

SummaryThe posterior dorsomedial striatum (pDMS) is necessary for goal-directed action, however the role of the direct (dSPN) and indirect (iSPN) spiny projection neurons in the pDMS in such action remains unclear. In this series of experiments, we examined the role of pDMS SPNs in goal-directed action and found that, whereas dSPNs were critical for goal-directed learning and for energizing the learned response, iSPNs were involved in updating that learning to support response flexibility. Instrumental training elevated expression of the plasticity marker Zif268 in dSPNs only, and chemogenetic suppression of dSPN activity during training prevented goal-directed learning. Unilateral optogenetic inhibition of dSPNs induced an ipsilateral response bias in goal-directed action performance. In contrast, although initial goal-directed learning was unaffected by iSPN manipulations, optogenetic inhibition of iSPNs, but not dSPNs, impaired the updating of this learning and attenuated response flexibility after changes in the action-outcome contingency.

Differential cortical activation of the striatal direct and indirect pathway cells: reconciling the anatomical and optogenetic results by using a computational method

2014 ◽  
Vol 112 (1) ◽  
pp. 120-146 ◽  
Author(s):  
Kenji Morita
Keyword(s):  
D2 Receptor ◽  
Computational Method ◽  
Cortical Activation ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Short Term ◽  
Apparent Contradiction ◽  
Striatal Projection Neurons ◽  
Cortical Inputs ◽  
Stimulation Of

The corticostriatal system is considered to be crucially involved in learning and action selection. Anatomical studies have shown that two types of corticostriatal neurons, intratelencephalic (IT) and pyramidal tract (PT) cells, preferentially project to dopamine D1 or D2 receptor-expressing striatal projection neurons, respectively. In contrast, an optogenetic study has shown that stimulation of IT axons evokes comparable responses in D1 and D2 cells and that stimulation of PT axons evokes larger responses in D1 cells. Since the optogenetic study applied brief stimulation only, however, the overall impacts of repetitive inputs remain unclear. Moreover, the apparent contradiction between the anatomical and optogenetic results remains to be resolved. I addressed these issues by using a computational approach. Specifically, I constructed a model of striatal response to cortical inputs, with parameters regarding short-term synaptic plasticity and anatomical connection strength for each connection type. Under the constraint of the optogenetic results, I then explored the parameters that best explain the previously reported paired-pulse ratio of response in D1 and D2 cells to cortical and intrastriatal stimulations, which presumably recruit different compositions of IT and PT fibers. The results indicate that 1) IT→D1 and PT→D2 connections are anatomically stronger than IT→D2 and PT→D1 connections, respectively, consistent with the previous findings, and that 2) IT→D1 and PT→D2 synapses entail short-term facilitation, whereas IT→D2 and PT→D1 synapses would basically show depression, and thereby 3) repetitive IT or PT inputs have larger overall impacts on D1 or D2 cells, respectively, supporting a recently proposed hypothesis on the roles of corticostriatal circuits in reinforcement learning.

scholarly journals The effects of chloride dynamics on substantia nigra pars reticulata responses to pallidal and striatal inputs

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ryan S Phillips ◽  
Ian Rosner ◽  
Aryn H Gittis ◽  
Jonathan E Rubin
Keyword(s):  
Substantia Nigra ◽  
Low Frequency ◽  
Operating Mode ◽  
Impact Behavior ◽  
Substantia Nigra Pars Reticulata ◽  
Indirect Pathway ◽  
Optogenetic Stimulation ◽  
Low Frequency Oscillations ◽  
Computational Work ◽  
Stimulation Of

As a rodent basal ganglia (BG) output nucleus, the substantia nigra pars reticulata (SNr) is well positioned to impact behavior. SNr neurons receive GABAergic inputs from the striatum (direct pathway) and globus pallidus (GPe, indirect pathway). Dominant theories of action selection rely on these pathways’ inhibitory actions. Yet, experimental results on SNr responses to these inputs are limited and include excitatory effects. Our study combines experimental and computational work to characterize, explain, and make predictions about these pathways. We observe diverse SNr responses to stimulation of SNr-projecting striatal and GPe neurons, including biphasic and excitatory effects, which our modeling shows can be explained by intracellular chloride processing. Our work predicts that ongoing GPe activity could tune the SNr operating mode, including its responses in decision-making scenarios, and GPe output may modulate synchrony and low-frequency oscillations of SNr neurons, which we confirm using optogenetic stimulation of GPe terminals within the SNr.

scholarly journals Linking emotional valence and anxiety in a mouse insula-amygdala circuit

2021 ◽  
Author(s):  
Céline Nicolas ◽  
Anes Ju ◽  
Yifan Wu ◽  
Hazim Eldirdiri ◽  
Sebastien Delcasso ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Insular Cortex ◽  
Emotional Valence ◽  
Projection Neurons ◽  
Negative Valence ◽  
Glutamatergic Neurons ◽  
Related Information ◽  
Starting Point ◽  
Positive And Negative Valence

Abstract The response of the insular cortex (IC) and amygdala to stimuli of positive and negative valence were found to be altered in patients with anxiety disorders. However, the coding properties of neurons controlling anxiety and valence remain unknown. Combining photometry recordings and chemogenetics in mice, we uncover the anxiogenic control of projection neurons in the anterior IC (aIC), independently of their projection target. Using viral tracing and ex vivo electrophysiology, we characterize the monosynaptic aIC to the basolateral amygdala (BLA) connection, and employed projection-specific optogenetics, to reveal anxiogenic properties of aIC-BLA neurons in anxiety-related behaviors. Finally, using photometry recordings, we identified that aIC-BLA neurons are active in anxiogenic spaces, and in response to aversive stimuli. Together, these findings show that negative valence, as well as anxiety-related information and behaviors, are encoded by aICBLA glutamatergic neurons, providing a starting point to understand how alterations of this pathway contribute to psychiatric disorders.

scholarly journals A computational model explains and predicts substantia nigra pars reticulata responses to pallidal and striatal inputs

2020 ◽  
Author(s):  
Ryan S. Phillips ◽  
Ian Rosner ◽  
Aryn H. Gittis ◽  
Jonathan E. Rubin
Keyword(s):  
Substantia Nigra ◽  
Low Frequency ◽  
Operating Mode ◽  
Impact Behavior ◽  
Substantia Nigra Pars Reticulata ◽  
Indirect Pathway ◽  
Optogenetic Stimulation ◽  
Low Frequency Oscillations ◽  
Computational Work ◽  
Stimulation Of

AbstractAs a rodent basal ganglia (BG) output nucleus, the substantia nigra pars reticulata (SNr) is well positioned to impact behavior. SNr neurons receive GABAergic inputs from the striatum (direct pathway) and globus pallidus (GPe, indirect pathway). Dominant theories of action selection rely on these pathways’ inhibitory actions. Yet, experimental results on SNr responses to these inputs are limited and include excitatory effects. Our study combines experimental and computational work to characterize, explain, and make predictions about these pathways. We observe diverse SNr responses to stimulation of SNr-projecting striatal and GPe neurons, including biphasic and excitatory effects, which our modeling shows can be explained by intracellular chloride processing. Our work predicts that ongoing GPe activity could tune the SNr operating mode, including its responses in decision-making scenarios, and GPe output may modulate synchrony and low-frequency oscillations of SNr neurons, which we confirm using optogenetic stimulation of GPe terminals within the SNr.

scholarly journals Opponent regulation of action performance and timing by striatonigral and striatopallidal pathways

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Konstantin I Bakhurin ◽  
Xiaoran Li ◽  
Alexander D Friedman ◽  
Nicholas A Lusk ◽  
Glenn DR Watson ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Reinforcement Schedule ◽  
Action Selection ◽  
Fixed Time ◽  
Indirect Pathway ◽  
Optogenetic Stimulation ◽  
Direct Pathway ◽  
Stimulation Of

The basal ganglia have been implicated in action selection and timing, but the relative contributions of the striatonigral (direct) and striatopallidal (indirect) pathways to these functions remain unclear. We investigated the effects of optogenetic stimulation of D1+ (direct) and A2A+ (indirect) neurons in the ventrolateral striatum in head-fixed mice on a fixed time reinforcement schedule. Direct pathway stimulation initiates licking, whereas indirect pathway stimulation suppresses licking and results in rebound licking after stimulation. Moreover, direct and indirect pathways also play distinct roles in timing. Direct pathway stimulation produced a resetting of the internal timing process, whereas indirect pathway stimulation transiently paused timing, and proportionally delayed the next bout of licking. Our results provide evidence for the continuous and opposing contributions of the direct and indirect pathways in the production and timing of reward-guided behavior.

scholarly journals Enhanced GABAergic Inhibition of Cholinergic Interneurons in the zQ175+/− Mouse Model of Huntington's Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Sean Austin O. Lim ◽  
D. James Surmeier
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Ex Vivo ◽  
Brain Slices ◽  
Projection Neurons ◽  
Gabaergic Inhibition ◽  
Indirect Pathway ◽  
Cholinergic Interneurons ◽  
Specific Alteration

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that initially manifests itself in the striatum. How intrastriatal circuitry is altered by the disease is poorly understood. To help fill this gap, the circuitry linking spiny projection neurons (SPNs) to cholinergic interneurons (ChIs) was examined using electrophysiological and optogenetic approaches in ex vivo brain slices from wildtype mice and zQ175+/− models of HD. These studies revealed a severalfold enhancement of GABAergic inhibition of ChIs mediated by collaterals of indirect pathway SPNs (iSPNs), but not direct pathway SPNs (dSPNs). This cell-specific alteration in synaptic transmission appeared in parallel with the emergence of motor symptoms in the zQ175+/− model. The adaptation had a presynaptic locus, as it was accompanied by a reduction in paired-pulse ratio but not in the postsynaptic response to GABA. The alterations in striatal GABAergic signaling disrupted spontaneous ChI activity, potentially contributing to the network dysfunction underlying the hyperkinetic phase of HD.

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.

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