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.

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 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.

Depression in the Direct Pathway of the Dorsomedial Striatum Permits the Formation of Habitual Action

2021 ◽  
Author(s):  
Xiaoxuan Yu ◽  
Shijie Chen ◽  
Qiang Shan
Keyword(s):  
Synaptic Plasticity ◽  
Dorsal Striatum ◽  
Excitatory Synapses ◽  
Indirect Pathway ◽  
Optimal Outcomes ◽  
Direct Pathway ◽  
Parallel Circuits ◽  
Directed Action ◽  
Action Strategies ◽  
Dorsomedial Striatum

Abstract In order to achieve optimal outcomes in an ever-changing environment, humans and animals generally manage their action control via either goal-directed action or habitual action. These two action strategies are thought to be encoded in distinct parallel circuits in the dorsal striatum, specifically, the posterior dorsomedial striatum (DMS) and the dorsolateral striatum (DLS), respectively. The striatum is primarily composed of two subtypes of medium spiny neurons (MSNs): the direct-pathway striatonigral and the indirect-pathway striatopallidal MSNs. MSN-subtype-specific synaptic plasticity in the DMS and the DLS has been revealed to underlie goal-directed action and habitual action, respectively. However, whether any MSN-subtype-specific synaptic plasticity in the DMS is associated with habitual action, and if so, whether the synaptic plasticity affects the formation of habitual action, are not known. This study demonstrates that postsynaptic depression in the excitatory synapses of the direct-pathway striatonigral MSNs in the DMS is formed after habit learning. Moreover, chemogenetically rescuing this depression compromises the acquisition, but not the expression, of habitual action. These findings reveal that an MSN-subtype-specific synaptic plasticity in the DMS affects habitual action and suggest that plasticity in the DMS as well as in the DLS contributes to the formation of habitual action.

scholarly journals Choice suppression is achieved through opponent but not independent function of the striatal indirect pathway in mice

2019 ◽  
Author(s):  
Kristen Delevich ◽  
Benjamin Hoshal ◽  
Anne GE Collins ◽  
Linda Wilbrecht
Keyword(s):  
Action Selection ◽  
Projection Neurons ◽  
Independent Function ◽  
Indirect Pathway ◽  
Successful Design ◽  
Freely Moving ◽  
Foraging Task ◽  
Simple Fashion ◽  
Dorsomedial Striatum

AbstractThe dorsomedial striatum (DMS) plays a key role in action selection, but little is known about how direct and indirect pathway spiny projection neurons (dSPNs and iSPNs) contribute to choice suppression in freely moving animals. Here, we used pathway-specific chemogenetic manipulation during a serial choice foraging task to test opposing predictions for iSPN function generated by two theories: 1) the ‘select/suppress’ heuristic which suggests iSPN activity is required to suppress alternate choices and 2) the network-inspired Opponent Actor Learning model (OpAL) which proposes that the weighted difference of dSPN and iSPN activity determines choice. We found that chemogenetic activation, but not inhibition, of iSPNs disrupted learned suppression of nonrewarded choices, consistent with the predictions of the OpAL model. Our findings suggest that iSPNs’ role in stopping and freezing does not extend in a simple fashion to choice suppression. These data may provide insights critical for the successful design of interventions for addiction or other conditions in which suppression of behavior is desirable.

scholarly journals Prepubertal ovariectomy alters dorsomedial striatum indirect pathway neuron excitability and explore/exploit balance in female mice

2021 ◽  
Author(s):  
Kristen Delevich ◽  
Christopher D. Hall ◽  
Linda Wilbrecht
Keyword(s):  
Behavioral Flexibility ◽  
Intrinsic Excitability ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Reversal Task ◽  
Female Mice ◽  
Sham Surgery ◽  
Hormonal Modulation ◽  
Choice Policy ◽  
Dorsomedial Striatum

Decision-making circuits are modulated across life stages (e.g. juvenile, adolescent, or adult)—as well as on the shorter timescale of reproductive cycles in females—to meet changing environmental and physiological demands. Ovarian hormonal modulation of relevant neural circuits is a potential mechanism by which behavioral flexibility is regulated in females. Here we examined the influence of prepubertal ovariectomy (pOVX) versus sham surgery on performance in an odor-based multiple choice reversal task. We observed that pOVX females made different types of errors during reversal learning compared to sham surgery controls. Using reinforcement learning models fit to trial-by-trial behavior, we found that pOVX females exhibited lower inverse temperature parameter (β) compared to sham females. These findings suggest that OVX females solve the reversal task using a more exploratory choice policy, whereas sham females use a more exploitative policy prioritizing estimated high value options. To seek a neural correlate of this behavioral difference, we performed whole-cell patch clamp recordings within the dorsomedial striatum (DMS), a region implicated in regulating action selection and explore/exploit choice policy. We found that the intrinsic excitability of dopamine receptor type 2 (D2R) expressing indirect pathway spiny projection neurons (iSPNs) was significantly higher in pOVX females compared to both unmanipulated and sham surgery females. Finally, to test whether mimicking this increase in iSPN excitability could recapitulate the pattern of reversal task behavior observed in pOVX females, we chemogenetically activated DMS D2R(+) neurons within intact female mice. We found that chemogenetic activation increased exploratory choice during reversal, similar to the pattern we observed in pOVX females. Together, these data suggest that pubertal status may influence explore/exploit balance in females via the modulation of iSPN intrinsic excitability within the DMS.

scholarly journals Complete representation of action space and value in all striatal pathways

2020 ◽  
Author(s):  
Moritz Weglage ◽  
Emil Wärnberg ◽  
Iakovos Lazaridis ◽  
Ourania Tzortzi ◽  
Konstantinos Meletis
Keyword(s):  
Large Scale ◽  
Dorsal Striatum ◽  
Action Space ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Complete Representation ◽  
Decision Variables ◽  
The Matrix ◽  
Action Value ◽  
Dorsomedial Striatum

ABSTRACTThe dorsal striatum plays a central role in motor and decision programs, such as the selection and execution of particular actions and the evaluation of their outcomes. A standard model has emerged where distinct output pathways encode separate motor-action signals, including selection-evaluation division in the matrix versus patch compartments. We used large-scale cell-type specific calcium imaging during motor and decision behaviors to determine and contrast the activity of individual striatal projection neurons (SPNs) belonging to one of the three major output pathways in the dorsomedial striatum – patch Oprm1+ SPNs versus the D1+ direct and A2A+ indirect pathway. We found that Oprm1+ SPNs were tuned to a number of different behavioral categories, such as to different movements, or to discrete actions and decisions in a two-choice task, and these complex representations were found to the same extent in all three striatal output pathways. The sharp tuning of individual SPNs was highly stereotyped over time while performing a specific task, but the tuning profile remapped between different behavioral contexts. In addition to action representations, SPNs showed pathway-independent representation of decision-variables such as the trial strategy and the action value. We propose that all three major output pathways in the dorsomedial striatum share a similarly complete representation of the entire action space, including task- and phase-specific signals of action value and choice.

The dorsomedial striatum: an optimal cellular environment for encoding and updating goal-directed learning

2021 ◽  
Vol 41 ◽  
pp. 38-44
Author(s):  
Bernard W Balleine ◽  
James Peak ◽  
Miriam Matamales ◽  
Jesus Bertran-Gonzalez ◽  
Genevra Hart
Keyword(s):  
Cellular Environment ◽  
Directed Learning ◽  
Dorsomedial Striatum

scholarly journals Job Seekers’ Self-Directed Learning Activities Explained Through the Lens of Regulatory Focus

2021 ◽  
pp. 089484532199164
Author(s):  
Adam M. Kanar ◽  
Dave Bouckenooghe
Keyword(s):  
Job Search ◽  
Regulatory Focus ◽  
Self Efficacy ◽  
Learning Activities ◽  
Job Seekers ◽  
Self Directed Learning ◽  
Significant Relationships ◽  
Directed Learning ◽  
Job Searching

This study aimed to understand the role of regulatory focus for influencing self-directed learning activities during a job search. The authors surveyed 185 job-searching university students at two time points to explore the conditions under which regulatory focus (promotion and prevention foci) impacts self-directed learning activities and the number of employment interviews secured. Both promotion and prevention foci showed significant relationships with self-directed learning activities and number of interviews, and positive and negative affect partially mediated these relationships. The relationships between both regulatory focus strategies and self-directed learning were also contingent on self-efficacy. More specifically, prevention focus and self-directed learning showed a positive relationship for job seekers with high levels of self-efficacy but a negative one for job seekers with low levels of self-efficacy. This research extends the understanding of the role of regulatory focus in the context of self-directed learning during a job search. Implications for research and practice are discussed.

Nitric oxide decreases lung liquid production via guanosine 3′,5′-cyclic monophosphate

2001 ◽  
Vol 280 (5) ◽  
pp. L923-L929 ◽  
Author(s):  
James J. Cummings ◽  
Huamei Wang
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Epithelium ◽  
Fetal Sheep ◽  
Cgmp Analog ◽  
Pulmonary Arterial ◽  
Series Of Experiments ◽  
Lung Liquid ◽  
Tracer Dilution ◽  
Induced Changes

We studied the role of cGMP in nitric oxide (NO)-induced changes in lung liquid production ( J v ) in chronically instrumented fetal sheep. Forty-five studies were done in which J v was measured by a tracer dilution technique. Left pulmonary arterial flow (Qlpa) was measured by a Doppler flow probe. There were two series of experiments. In the first, we gave 8-bromo-cGMP, a cGMP analog, by either the pulmonary vascular or intraluminal route; in the second, we used agents to inhibit or enhance endogenous cGMP activity. When infused directly into the pulmonary circulation, 8-bromo-cGMP significantly increased Qlpa but had no effect on J v. Conversely, when instilled into the lung liquid, 8-bromo-cGMP had no effect on Qlpa but significantly reduced J v. Inhibition of guanylate cyclase activity with methylene blue totally blocked, whereas phosphodiesterase inhibition with Zaprinast significantly enhanced, the effect of instilled NO on J v. Thus the reduction in lung liquid caused by NO appears to be mediated by cGMP, perhaps through a direct effect on the pulmonary epithelium.

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