Vol 22, No 9 (2024)

The motor areas of the cortex and the basal ganglia both contribute to determining which motor actions will be recruited at any moment in time, and their functions are intertwined. Here, we review the basal ganglia mechanisms underlying the selection of behavior of the downstream control of motor centers in the midbrain and brainstem and show that the basic organization of the forebrain motor system is evolutionarily conserved throughout vertebrate phylogeny. The output level of the basal ganglia (e.g. substantia nigra pars reticulata) has GABAergic neurons that are spontaneously active at rest and inhibit a number of specific motor centers, each of which can be relieved from inhibition if the inhibitory output neurons themselves become inhibited. The motor areas of the cortex act partially via the dorsolateral striatum (putamen), which has specific modules for the forelimb, hindlimb, trunk, etc. Each module operates in turn through the two types of striatal projection neurons that control the output modules of the basal ganglia and thereby the downstream motor centers. The mechanisms for lateral inhibition in the striatum are reviewed as well as other striatal mechanisms contributing to action selection. The motor cortex also exerts a direct excitatory action on specific motor centers. An overview is given of the basal ganglia control exerted on the different midbrain/brainstem motor centers, and the efference copy information fed back via the thalamus to the striatum and cortex, which is of importance for the planning of future movements.

Although classically considered a relay station for basal ganglia (BG) output, the anatomy, connectivity, and function of the mesencephalic locomotor region (MLR) were redefined during the last two decades. In striking opposition to what was initially thought, MLR and BG are actually reciprocally and intimately interconnected. New viral-based, optogenetic, and mapping technologies revealed that cholinergic, glutamatergic, and GABAergic neurons coexist in this structure, which, in addition to extending descending projections, send long-range ascending fibers to the BG. These MLR projections to the BG convey motor and non-motor information to specific synaptic targets throughout different nuclei. Moreover, MLR efferent fibers originate from precise neuronal subpopulations located in particular MLR subregions, defining independent anatomo-functional subcircuits involved in particular aspects of animal behavior such as fast locomotion, explorative locomotion, posture, forelimb- related movements, speed, reinforcement, among others. In this review, we revised the literature produced during the last decade linking MLR and BG. We conclude that the classic framework considering the MLR as a homogeneous output structure passively receiving input from the BG needs to be revisited. We propose instead that the multiple subcircuits embedded in this region should be taken as independent entities that convey relevant and specific ascending information to the BG and, thus, actively participate in the execution and tuning of behavior.

Individuals often learn how to perform new actions for particular outcomes against a complex background of existing action-outcome associations. As such, this new knowledge can interfere or even compete with existing knowledge, such that individuals must use internal and external cues to determine which action is appropriate to the current situation. The question thus remains as to how this problem is solved at a neural level. Research over the last decade or so has begun to determine how the brain achieves situation-appropriate action selection. Several converging lines of evidence suggest that it is achieved through the complex interactions of acetylcholine and dopamine within the striatum in a manner that relies on glutamatergic inputs from the cortex and thalamus. Here we briefly review this evidence, then relate it to several very recent findings to provide new, speculative insights regarding the precise nature of striatal acetylcholine/dopamine interaction dynamics and their relation to situation-appropriate action selection.

Background:Regional changes in corticostriatal transmission induced by phasic dopaminergic signals are an essential feature of the neural network responsible for instrumental reinforcement during discovery of an action. However, the timing of signals that are thought to contribute to the induction of corticostriatal plasticity is difficult to reconcile within the framework of behavioural reinforcement learning, because the reinforcer is normally delayed relative to the selection and execution of causally-related actions.

Objective:While recent studies have started to address the relevance of delayed reinforcement signals and their impact on corticostriatal processing, our objective was to establish a model in which a sensory reinforcer triggers appropriately delayed reinforcement signals relayed to the striatum via intact neuronal pathways and to investigate the effects on corticostriatal plasticity.

Methods:We measured corticostriatal plasticity with electrophysiological recordings using a light flash as a natural sensory reinforcer, and pharmacological manipulations were applied in an in vivo anesthetized rat model preparation.

Results:We demonstrate that the spiking of striatal neurons evoked by single-pulse stimulation of the motor cortex can be potentiated by a natural sensory reinforcer, operating through intact afferent pathways, with signal timing approximating that required for behavioural reinforcement. The pharmacological blockade of dopamine receptors attenuated the observed potentiation of corticostriatal neurotransmission.

Conclusion:This novel in vivo model of corticostriatal plasticity offers a behaviourally relevant framework to address the physiological, anatomical, cellular, and molecular bases of instrumental reinforcement learning.

Background:The pedunculopontine nucleus (PPN) maintains a bidirectional connectivity with the basal ganglia that supports their shared roles in the selection and execution of motor actions. Previous studies identified a role for PPN neurons in goal-directed behavior, but the cellular substrates underlying this function have not been elucidated. We recently revealed the existence of a monosynaptic GABAergic input from the PPN that inhibits dopamine neurons of the substantia nigra. Activation of this pathway interferes with the execution of learned motor sequences when the actions are rewarded, even though the inhibition of dopamine neurons did not shift the value of the action, hence suggesting executive control over the gating of behavior.

Objective:To test the attributes of the inhibition of dopamine neurons by the PPN in the context of goal-directed behavior regardless of whether the outcome is positive or negative.

Methods:We delivered optogenetic stimulation to PPN GABAergic axon terminals in the substantia nigra during a battery of behavioral tasks with positive and negative valence.

Results:Inhibition of dopamine neurons by PPN optogenetic activation during an appetitive task impaired the initiation and overall execution of the behavioral sequence without affecting the consumption of reward. During an active avoidance task, the same activation impaired the ability of mice to avoid a foot shock, but their escape response was unaffected. In addition, responses to potential threats were significantly attenuated.

Conclusion:Our results show that PPN GABAergic neurons modulate learned, goal-directed behavior of unsigned valence without affecting overall motor behavior.

Background:Cholinergic interneurons (ChIs) are important for learning and memory. They exhibit a multiphasic excitation-pause-rebound response to reward or sensory cues indicating a reward, believed to gate dopamine-dependent learning. Although ChIs receive extensive top-down inputs from the cortex and bottom-up inputs from the thalamus and midbrain, it is unclear which inputs are involved in the development of ChI multiphasic activity.

Methods:We used a single-unit recording of putative ChIs (pChIs) in response to cortical and visual stimulation to investigate how top-down and bottom-up inputs regulate the firing pattern of ChIs.

Results:We demonstrated that cortical stimulation strongly regulates pChIs, with the maximum firing rate occurring at the peak of the inverted local field potential (iLFP), reflecting maximum cortical stimulation. Pauses in pChIs occurred during the descending phase of iLFP, indicating withdrawal of excitatory cortical input. Visual stimulation induced long pauses in pChIs, but it is unlikely that bottom- up inputs alone induce pauses in behaving animals. Also, the firing pattern of ChIs triggered by visual stimulation did not correlate with the iLFP as it did after cortical stimulation. Top-down and bottom-up inputs independently regulate the firing pattern of ChIs with similar efficacy but notably produce a well-defined pause in ChI firing.

Conclusion:This study provides in vivo evidence that the multiphasic ChI response may require both top-down and bottom-up inputs. The findings suggest that the firing pattern of ChIs correlated to the iLFP might be a useful tool for estimating the degree of contribution of top-down and bottom-up inputs in regulating the firing activity of ChIs.