A spiking computational model for striatal cholinergic interneurons.

Cholinergic interneurons in the striatum, also known as tonically active interneurons or TANs, are thought to have a strong effect on corticostriatal plasticity and on striatal activity and outputs, which in turn play a critical role in modulating downstream basal ganglia activity and movement. Striatal TANs can exhibit a variety of firing patterns and responses to synaptic inputs; furthermore, they have been found to display various surges and pauses in activity associated with sensory cues and reward delivery in learning as well as with motor tic production. To help explain the factors that contribute to TAN activity patterns and to provide a resource for future studies, we present a novel conductance-based computational model of a striatal TAN. We show that this model produces the various characteristic firing patterns observed in recordings of TANs. With a single baseline tuning associated with tonic firing, the model also captures a wide range of TAN behaviors found in previous experiments involving a variety of manipulations. In addition to demonstrating these results, we explain how various ionic currents in the model contribute to them. Finally, we use this model to explore the contributions of the acetylcholine released by TANs to the production of surges and pauses in TAN activity in response to strong excitatory inputs. These results provide predictions for future experimental testing that may help with efforts to advance our understanding of the role of TANs in reinforcement learning and in motor disorders such as Tourette's syndrome.

The roles of ascending sensory signals and top-down central control in the entrainment of a locomotor CPG.

Previous authors have proposed two basic hypotheses about the factors that form the basis of locomotor rhythms in walking insects: sensory feedback only or sensory feedback together with rhythmic activity of small neural circuits called central pattern generators (CPGs). Here we focus on the latter. Following this concept, to generate functional outputs, locomotor control must feature both rhythm generation by CPGs at the level of individual joints and coordination of their rhythmic activities, so that all muscles are activated in an appropriate pattern. This work provides an in-depth analysis of an aspect of this coordination process based on an existing network model of stick insect locomotion. Specifically, we consider how the control system for a single joint in the stick insect leg may produce rhythmic output when subjected to ascending sensory signals from other joints in the leg. In this work, the core rhythm generating CPG component of the joint under study is represented by a classical half-center oscillator constrained by a basic set of experimental observations. While the dynamical features of this CPG, including phase transitions by escape and release, are well understood, we provide novel insights about how these transition mechanisms yield entrainment to the incoming sensory signal, how entrainment can be lost under variation of signal strength and period or other perturbations, how entrainment can be restored by modulation of tonic top-down drive levels, and how these factors impact the duty cycle of the motor output.

Neural activity during a simple reaching task in macaques is counter to gating and rebound in basal ganglia-thalamic communication.

Task-related activity in the ventral thalamus, a major target of basal ganglia output, is often assumed to be permitted or triggered by changes in basal ganglia activity through gating- or rebound-like mechanisms. To test those hypotheses, we sampled single-unit activity from connected basal ganglia output and thalamic nuclei (globus pallidus-internus [GPi] and ventrolateral anterior nucleus [VLa]) in monkeys performing a reaching task. Rate increases were the most common peri-movement change in both nuclei. Moreover, peri-movement changes generally began earlier in VLa than in GPi. Simultaneously recorded GPi-VLa pairs rarely showed short-time-scale spike-to-spike correlations or slow across-trials covariations, and both were equally positive and negative. Finally, spontaneous GPi bursts and pauses were both followed by small, slow reductions in VLa rate. These results appear incompatible with standard gating and rebound models. Still, gating or rebound may be possible in other physiological situations: simulations show how GPi-VLa communication can scale with GPi synchrony and GPi-to-VLa convergence, illuminating how synchrony of basal ganglia output during motor learning or in pathological conditions may render this pathway effective. Thus, in the healthy state, basal ganglia-thalamic communication during learned movement is more subtle than expected, with changes in firing rates possibly being dominated by a common external source.