JOURNAL CLUBS
May 14th, 2024 - 1.00 pm CET
Presented by :Anne Buot, Paris Brain Institute (ICM), NERB team, Paris
Authors : Young-Hoon Nho, Camarin E. Rolle, Uros Topalovic, Rajat S. Shivacharan, Tricia N. Cunningham, Sonja Hiller,
Daniel Batista, Austin Feng, Flint M. Espil, Ian H. Kratter, Mahendra T. Bhati, Marissa Kellogg, Ahmed M. Raslan,
Nolan R. Williams, John Garnett, Bijan Pesaran, Desmond J. Oathes, Nanthia Suthana, Daniel A.N. Barbosa,
and Casey H. Halpern
Published in : Neuron 112, 73-83, Jan 3, 2024. doi: 10.1016/j.neuron.2023.09.034
Weblink : Neuron website
Summary:
Treatment-resistant obsessive-compulsive disorder (OCD) occurs in approximately one-third of OCD patients. Obsessions may fluctuate over time but often occur or worsen in the presence of internal (emotional state and thoughts) and external (visual and tactile) triggering stimuli. Obsessive thoughts and related compulsive urges fluctuate (are episodic) and so may respond well to a time-locked brain stimulation strategy sensitive and responsive to these symptom fluctuations. Early evidence suggests that neural activity can be captured from ventral striatal regions implicated in OCD to guide such a closed-loop approach. Here, we report on a first-in-human application of responsive deep brain stimulation (rDBS) of the ventral striatum for a treatment-refractory OCD individual who also had comorbid epilepsy. Self-reported obsessive symptoms and provoked OCD-related distress correlated with ventral striatal electrophysiology. rDBS detected the time-domain area-based feature from invasive electroencephalography low-frequency oscillatory power fluctuations that triggered bursts of stimulation to ameliorate OCD symptoms in a closed-loop fashion. rDBS provided rapid, robust, and durable improvement in obsessions and compulsions. These results provide proof of concept for a personalized, physiologically guided DBS strategy for OCD.
March 21st, 2024 - 12.30 pm CET
Presented by :Abderrahman Fettah, Institut des Maladies Dégénératives (IMN), Bordeaux
Authors : Jared M Cregg, Simrandeep K Sidhu, Roberto Leiras, Ole Kiehn
Published in : Nat Neurosci. 2024 Feb 12. doi: 10.1038/s41593-024-01569-8
Weblink : https://www.nature.com/articles/s41593-024-01569-8
Summary:
The basal ganglia are essential for executing motor actions. How the basal ganglia engage spinal motor networks has remained elusive. Medullary Chx10 gigantocellular (Gi) neurons are required for turning gait programs, suggesting that turning gaits organized by the basal ganglia are executed via this descending pathway. Performing deep brainstem recordings of Chx10 Gi Ca2+ activity in adult mice, we show that striatal projection neurons initiate turning gaits via a dominant crossed pathway to Chx10 Gi neurons on the contralateral side. Using intersectional viral tracing and cell-type-specific modulation, we uncover the principal basal ganglia-spinal cord pathway for locomotor asymmetries in mice: basal ganglia → pontine reticular nucleus, oral part (PnO) → Chx10 Gi → spinal cord. Modulating the restricted PnO → Chx10 Gi pathway restores turning competence upon striatal damage, suggesting that dysfunction of this pathway may contribute to debilitating turning deficits observed in Parkinson's disease. Our results reveal the stratified circuit architecture underlying a critical motor program.
January 30th, 2024 - 12.30 pm CET
Article : Striatal dopamine integrates cost, benefit, and motivation
Presented by : Dr. Enrica Montalban, Dr. Fabien Ducrocq, NutriNeuro Lab, Bordeaux
Authors : Neir Eshel, Gavin C Touponse, Allan R Wang, Amber K Osterman, Amei N Shank, Alexandra M Groome Lara Taniguchi, Daniel F Cardozo Pinto, Jason Tucciarone, Brandon S Bentzley, Robert C Malenka
Published in : Neuron. 2023 Nov 16:S0896-6273(23)00843-7
Weblink : 10.1016/j.neuron.2023.10.038
Summary:
Striatal dopamine (DA) release has long been linked to reward processing, but it remains controversial whether DA release reflects costs or benefits and how these signals vary with motivation. Here, we measure DA release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) while independently varying costs and benefits and apply behavioral economic principles to determine a mouse's level of motivation. We reveal that DA release in both structures incorporates both reward magnitude and sunk cost. Surprisingly, motivation was inversely correlated with reward-evoked DA release. Furthermore, optogenetically evoked DA release was also heavily dependent on sunk cost. Our results reconcile previous disparate findings by demonstrating that striatal DA release simultaneously encodes cost, benefit, and motivation but in distinct manners over different timescales. Future work will be necessary to determine whether the reduction in phasic DA release in highly motivated animals is due to changes in tonic DA levels.
JOURNAL CLUBS
You can acces it here: link
December 8th, 2023 - 12:45pm CET
Article : Spontaneous behaviour is structured by reinforcement without explicit reward
Presented by : Juliette Contadini et Maud Schaffhauser, INMED, Marseille
Authors : Jeffrey E. Markowitz, Winthrop F. Gillis, Maya Jay, Jeffrey Wood, Ryley W. Harris, Robert Cieszkowski, Rebecca Scott, David Brann, Dorothy Koveal, Tomasz Kula, Caleb Weinreb, Mohammed Abdal Monium Osman, Sandra Romero Pinto, Naoshige Uchida, Scott W. Linderman, Bernardo L. Sabatini & Sandeep Robert Datta
Published in : Nature volume 614, pages 108–117 (2023) -
Weblink : https://www.nature.com/articles/s41586-022-05611-2
Summary:
Spontaneous animal behaviour is built from action modules that are concatenated by the brain into sequences1,2. However, the neural mechanisms that guide the composition of naturalistic, self-motivated behaviour remain unknown. Here we show that dopamine systematically fluctuates in the dorsolateral striatum (DLS) as mice spontaneously express sub-second behavioural modules, despite the absence of task structure, sensory cues or exogenous reward. Photometric recordings and calibrated closed-loop optogenetic manipulations during open field behaviour demonstrate that DLS dopamine fluctuations increase sequence variation over seconds, reinforce the use of associated behavioural modules over minutes, and modulate the vigour with which modules are expressed, without directly influencing movement initiation or moment-to-moment kinematics. Although the reinforcing effects of optogenetic DLS dopamine manipulations vary across behavioural modules and individual mice, these differences are well predicted by observed variation in the relationships between endogenous dopamine and module use. Consistent with the possibility that DLS dopamine fluctuations act as a teaching signal, mice build sequences during exploration as if to maximize dopamine. Together, these findings suggest a model in which the same circuits and computations that govern action choices in structured tasks have a key role in sculpting the content of unconstrained, high-dimensional, spontaneous behaviour.
