scholarly journals Opposing roles of the dorsolateral and dorsomedial striatum in the acquisition of skilled action sequencing

2021 ◽  
Author(s):  
Karly M. Turner ◽  
Anna Svegborn ◽  
Mia Langguth ◽  
Colin McKenzie ◽  
Trevor W. Robbins
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Orbitofrontal Cortex ◽  
Habit Formation ◽  
Loss Of Function ◽  
Dorsolateral Striatum ◽  
Cortical Inputs ◽  
Action Sequencing ◽  
Sequencing Task ◽  
Dorsomedial Striatum

AbstractThe shift in control from dorsomedial to dorsolateral striatum during skill and habit formation is well established, but whether striatal subregions orchestrate this shift co-operatively or competitively remains unclear. Cortical inputs have also been implicated in the shift towards automaticity. Do cortical inputs mirror their downstream striatal targets across this transition? We addressed these questions using a five-step heterogeneous action sequencing task that is optimally performed by automated chains of actions. By optimising automatic responding, we discovered that loss of function in the dorsomedial striatum accelerated acquisition. In contrast, loss of function in the dorsolateral striatum impeded acquisition of sequencing, demonstrating functional opposition within the striatum. Unexpectedly the medial prefrontal cortex was not involved, however the lateral orbitofrontal cortex was critical. These results shift current theories about striatal control of behaviour to a model of competitive opposition, where the dorsomedial striatum acts in a gating role to inhibit dorsolateral-driven behaviour.

Haploinsufficiency of Tsc2 Leads to Hyperexcitability of Medial Prefrontal Cortex via Weakening of Tonic GABAB Receptor-mediated Inhibition

2020 ◽  
Vol 30 (12) ◽  
pp. 6313-6324
Author(s):  
Davide Bassetti ◽  
Aniello Lombardi ◽  
Sergei Kirischuk ◽  
Heiko J Luhmann
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Tumor Suppressor Genes ◽  
Time Window ◽  
Gabab Receptor ◽  
Brain Slices ◽  
Autism Spectrum ◽  
Loss Of Function ◽  
Electrophysiological Recordings ◽  
Spectrum Disorders

Abstract Loss-of-function mutation in one of the tumor suppressor genes TSC1 or TSC2 is associated with several neurological and psychiatric diseases, including autism spectrum disorders (ASDs). As an imbalance between excitatory and inhibitory neurotransmission, E/I ratio is believed to contribute to the development of these disorders, we investigated synaptic transmission during the first postnatal month using the Tsc2+/− mouse model. Electrophysiological recordings were performed in acute brain slices of medial prefrontal cortex. E/I ratio at postnatal day (P) 15–19 is increased in Tsc2+/− mice as compared with wildtype (WT). At P25–30, facilitated GABAergic transmission reduces E/I ratio to the WT level, but weakening of tonic GABAB receptor (GABABR)-mediated inhibition in Tsc2+/− mice leads to hyperexcitability both at single cell and neuronal network level. Short (1 h) preincubation of P25–30 Tsc2+/− slices with baclofen restores the GABABR-mediated inhibition and reduces network excitability. Interestingly, the same treatment at P15–19 leads to weakening of GABABR-mediated inhibition. We hypothesize that a dysfunction of tonic GABABR-mediated inhibition might contribute to the development of ASD symptoms and suggest that GABABR activation within an appropriate time window may be considered as a therapeutic target in ASD.

scholarly journals A thalamocortical circuit for updating action-outcome associations

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Virginie Fresno ◽  
Shauna L Parkes ◽  
Angélique Faugère ◽  
Etienne Coutureau ◽  
Mathieu Wolff
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Orbitofrontal Cortex ◽  
Instrumental Performance ◽  
Adaptive Responding ◽  
The Impact ◽  
Adaptive Decision Making ◽  
Cardinal Feature ◽  
Outcome Devaluation

The ability to flexibly use knowledge is one cardinal feature of goal-directed behaviors. We recently showed that thalamocortical and corticothalamic pathways connecting the medial prefrontal cortex and the mediodorsal thalamus (MD) contribute to adaptive decision-making (Alcaraz et al., 2018). In this study, we examined the impact of disconnecting the MD from its other main cortical target, the orbitofrontal cortex (OFC) in a task assessing outcome devaluation after initial instrumental training and after reversal of action-outcome contingencies. Crossed MD and OFC lesions did not impair instrumental performance. Using the same approach, we found however that disconnecting the OFC from its other main thalamic afferent, the submedius nucleus, produced a specific impairment in adaptive responding following action-outcome reversal. Altogether, this suggests that multiple thalamocortical circuits may act synergistically to achieve behaviorally relevant functions.

scholarly journals Altered Functional Segregated Sensorimotor, Associative, and Limbic Cortical-Striatal Connections in Parkinson's Disease: An fMRI Investigation

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao-Mian Mi ◽  
Wei Zhang ◽  
Yu Li ◽  
Ai-Ping Liu ◽  
Zhi-Li Ren ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Basal Ganglia ◽  
Functional Connectivity ◽  
Sensorimotor Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Disease Duration ◽  
Dorsolateral Striatum ◽  
Sensorimotor Loop ◽  
Dorsolateral Prefrontal ◽  
Dorsomedial Striatum

Multiple studies have identified segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. It has been suggested that in PD, preferential loss of dopamine in the posterior putamen may cause a major deficit in habitual control (mediated by the sensorimotor cortical-striatal loop), and the patients may therefore be forced into a progressive reliance on the goal-directed behavior (regulated by the associative cortical-striatal loop). Functional evidence supporting this point is scarce at present. This study aims to verify the functional connectivity changes within the sensorimotor, associative, and limbic cortical-striatal loops in PD. Resting-state fMRI of 70 PD patients and 30 controls were collected. Bilateral tripartite functional territories of basal ganglia and their associated cortical structures were chosen as regions of interest, including ventral striatum and ventromedial prefrontal cortex for limbic loop; dorsomedial striatum and dorsolateral prefrontal cortex for associative loop; dorsolateral striatum and sensorimotor cortex for sensorimotor loop. Pearson's correlation coefficients for each seed pair were calculated to obtain the functional connectivity. The relationships between functional connectivity and disease severity were further investigated. Functional connectivity between dorsolateral striatum and sensorimotor cortex is decreased in PD patients, and negatively correlated with disease duration; whereas functional connectivity between dorsomedial striatum and dorsolateral prefrontal cortex is also decreased but postitively correlated with disease duration. The functional connectivity within the sensorimotor loop is pathologically decreased in PD, while the altered connectivity within the associative loop may indicate a failed attempt to compensate for the loss of connectivity within the sensorimotor loop.

scholarly journals The Imposition of Value on Odor: Transient and Persistent Representations of Odor Value in Prefrontal Cortex

2019 ◽  
Author(s):  
Peter Y. Wang ◽  
Cristian Boboila ◽  
Philip Shamash ◽  
Zheng Wu ◽  
Nicole P Stein ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Neural Activity ◽  
Orbitofrontal Cortex ◽  
Internal State ◽  
Brain Structures ◽  
Olfactory Cortex ◽  
Conditioned Stimuli ◽  
Photon Imaging

SUMMARYThe representation of odor in olfactory cortex (piriform) is distributive and unstructured and can only be afforded behavioral significance upon learning. We performed 2-photon imaging to examine the representation of odors in piriform and in two downstream stations, the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), as mice learned olfactory associations. In piriform we observed minor changes in neural activity unrelated to learning. In OFC, 30% of the neurons acquired robust responses to conditioned stimuli (CS+) after learning, and these responses were gated by context and internal state. The representation in OFC, however, diminished after learning and persistent representations of CS+ and CS− odors emerged in mPFC. Optogenetic silencing indicates that these two brain structures function sequentially to consolidate the learning of appetitive associations. These data demonstrate the transformation of a representation of odor identity in piriform into transient and persistent representations of value in the prefrontal cortex.

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