Friday · Oct 9
9:00 - 11:00

Balancing movement: exploring dichotomies in neural circuits for action

Maria Soledad Esposito

Centro Atómico Bariloche, Comisión Nacional de Energía Atómica (CNEA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)

Nicolas Andres Morgenstern

Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal

Accurate and timely actions allow animals to survive in an always dynamic and challenging environment. The central nervous system (CNS) plays a central role in this process by precisely orchestrating movements. Along the CNS, the regulation of motor behavior relays on a delicate balance between antagonistic but complementary systems. Perturbations in this tight balance, usually lead to motor disfunction. In this symposium, we propose to explore four dichotomic circuits underlying motor behavior: direct vs. indirect striatal output pathways; intratelencephalic vs. pyramidal tract corticostriatal connections; movement vs. reward coding in the striatum; and plasticity of excitatory vs. inhibitory spinal cord interneurons. We expect, that altogether, the results presented here provide a general perspective on how circuits ranging from the cortex to the spinal cord, act in constant balance to support successful movement.

Theta oscillations in the dorsal striatum signal reward in a virtual reality navigation task

Camila L. Zold

Instituto de Fisiología y Biofísica (IFIBIO) Houssay, CONICET - Universidad de Buenos Aires, Buenos Aires, Argentina.

The striatum (STR) is important for aspects of learning like the use of reinforcement information to bias subsequent action selection. In particular, STR oscillations are known to be modulated during learning and space navigation tasks, and they may contribute to information processing between brain areas. However, little is known about the role of STR local field potential (LFP) oscillations in reward signaling. Using a virtual reality task, we studied if STR oscillations are involved in reward signaling. Thus, we trained head-fixed mice to explore and obtain rewards in a virtual linear track. The track consisted of rewarded areas separated by unrewarded corridors. A sequence of licks was required to obtain a reward upon reaching a rewarded area. Once animals were familiarized with the task, we included 20% omissions. We used an array of four chronically implanted tetrodes to record single unit and LFP activity in the dorsomedial STR of mice performing this task. We found a strong modulation of theta oscillations during the task associated with reward consumption. Interestingly, this increase in theta power was absent if reward is omitted. Also, we found that a high proportion of striatal neurons were phase-locked to the theta rhythm and responded to different events in the task. Using a local STR reference for LFP recordings showed that reward induced theta modulations were still present, suggesting a local origin and a possible role in circuit-level codification of reward.

Contribution of the basal ganglia pathways on the initiation and execution of motor sequences

Fatuel Tecuapetla

Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico

The performance of an action relies on the initiation and execution of appropriate movement sequences. Two basal ganglia pathways have been classically hypothesized to regulate this process via opposing roles in movement facilitation and suppression. By using a series of state-dependent optogenetic manipulations, we interrogated the contributions of each pathway and found that both the direct striatonigral pathway and the indirect striatopallidal pathway are necessary for smooth initiation and the execution of learned action sequences. In an attempt to identify the contribution of the excitatory inputs to these pathways we also manipulated their thalamic and cortical inputs uncovering specific subcircuits contribution during the initiation, execution, and structuration of motor sequences.

Pyramidal tract neurons drive corticostriatal feed-forward excitation through cholinergic interneurons

Nicolas Andres Morgenstern

Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal

The striatum is composed of medium spiny neurons (MSNs), the only neuronal subtype projecting outside this structure, and small populations of GABA- or acetylcholine-releasing interneurons. These sparse interneurons can broadly modulate MSNs input integration and spiking, controlling striatal output. The main excitatory input to the striatum arises from two corticostriatal populations: intratelencephalic (IT) and pyramidal tract (PT) neurons. However, their specific connectivity to striatal interneurons, as well as the polysynaptic impact that pathway-specific activation has on MSN computations, remains underexplored. Here, using slice electrophysiology, optogenetics and transgenic mice, we found that the activation of PT evokes biphasic signals in MSNs, by eliciting a second excitatory phase impinging immediately after direct corticostriatal excitation. This delayed phase is mediated by striatal cholinergic interneurons that are efficiently recruited by PT, but not by IT inputs. Thus, PT afferents, by selectively activating local microcircuit players, trigger acetylcholine-dependent striatal events, conveying feed-forward excitation to MSNs.

Learning to walk without the brain: Spinal excitatory interneurons define age-dependent locomotor circuit plasticity

Aya Takeoka

Neuroelectronics Research Flanders, VIB, KU Leuven

While severe spinal cord injury to a mature nervous system often leads to irreversible paralysis, neonatal rodents receiving a complete injury at thoracic level demonstrate as adults proficient hindlimb locomotion without re-establishment of connection to the brain. However, how the spinal cord achieves such autonomous functionality remains obscure. Using neurotransmitter identity and developmental origin as criteria, we uncover that age of injury impacts excitatory/inhibitory (E/I) circuit balance by affecting survival, connectivity and neurotransmitter phenotype switching of defined excitatory interneuron subpopulations, but not inhibitory cohorts. Concomitant proprioceptive afferent (PA) ablation with neonatal injury leads to paralysis and disrupts E/I circuit balance. While movement-directed augmentation of PA-activity or viral intervention partially restore E/I balance shift, mice receiving injury as adults never regain control of hindlimb movement. Together, our study implicates that both activities of PAs and cell-intrinsic plasticity at the time of injury shape autonomy of spinal circuit to walk without the brain.