It is widely accepted that the basal ganglia (BG) play a key role in action selection and reinforcement learning. However, despite considerable number of studies, the BG architecture and function are not completely understood. Action selection and reinforcement learning are facilitated by the activity of dopaminergic neurons, which encode reward prediction errors when reward outcomes are higher or lower than expected. The BG are thought to select proper motor responses by gating appropriate actions, and suppressing inappropriate ones. The direct striato-nigral (GO) and the indirect striato-pallidal (NOGO) pathways have been suggested to provide the functions of BG in the two-pathway concept. Previous models confirmed the idea that these two pathways can mediate the behavioral choice, but only for a relatively small number of potential behaviors. Recent studies have provided new evidence of BG involvement in motor adaptation tasks, in which adaptation occurs in a non-error-based manner. In such tasks, there is a continuum of possible actions, each represented by a complex neuronal activity pattern. We extended the classical concept of the two-pathway BG by creating a model of BG interacting with a movement execution system, which allows for an arbitrary number of possible actions. The model includes sensory and premotor cortices, BG, a spinal cord network, and a virtual mechanical arm performing 2D reaching movements. The arm is composed of 2 joints (shoulder and elbow) controlled by 6 muscles (4 mono-articular and 2 bi-articular). The spinal cord network contains motoneurons, controlling the muscles, and sensory interneurons that receive afferent feedback and mediate basic reflexes. Given a specific goal-oriented motor task, the BG network through reinforcement learning constructs a behavior from an arbitrary number of basic actions represented by cortical activity patterns. Our study confirms that, with slight modifications, the classical two-pathway BG concept is consistent with results of previous studies, including non-error based motor adaptation experiments, pharmacological manipulations with BG nuclei, and functional deficits observed in BG-related motor disorders.
Cutaneous sensory feedback from the paw pads plays an important role in regulating body balance, especially in challenging environments like ladder or slope walking. Here, we investigated the contribution of cutaneous sensory feedback from the paw pads to balance control in cats stepping on a split-belt treadmill. Fore- and hindpaws were anesthetized unilaterally using lidocaine injections. We evaluated body balance in intact and compromised cutaneous feedback conditions during split-belt locomotion with belt speed ratios of 0.5, 1.0, 1.5 and 2.0. Measures of body balance included step width, relative duration of limb support phases, lateral bias of center of mass (CoM) and margins of static and dynamic stability. In the intact condition, static and dynamic balance declined with increasing belt-speed ratio due to a lateral shift of the CoM toward the borders of support on the slower moving belt. Anesthesia of the ipsilateral paws improved locomotor balance with increasing belt speed ratios by reversing the CoM shift, decreasing the relative duration of the two-limb support phase, increasing the duration of four- or three-limb support phases, increasing the hindlimb step width and static stability. We observed no changes in most balance measures in anesthetized conditions during tied-belt locomotion at 0.4 m s−1. CoM lateral displacements closely resembled those of the inverted pendulum and of human walking. We propose that unilaterally compromised cutaneous feedback from the paw pads is compensated by improving lateral balance and by shifting the body toward the anesthetized paws to increase tactile sensation during the stance phase.
Rhythmic limb movements during locomotion are controlled by central pattern generator (CPG) circuits located in the spinal cord. It is considered that these circuits are composed of individual rhythm generators (RGs) for each limb interacting with each other through multiple commissural and long propriospinal circuits. The organization and operation of each RG are not fully understood, and different competing theories exist about interactions between its flexor and extensor components, as well as about leftright commissural interactions between the RGs. The central idea of circuit organization proposed in this study is that with an increase of excitatory input to each RG (or an increase in locomotor speed) the rhythmogenic mechanism of the RGs changes from "flexor-driven" rhythmicity to a "classical half-center" mechanism. We test this hypothesis using our experimental data on changes in duration of stance and swing phases in the intact and spinal cats walking on the ground or tied-belt treadmills (symmetric conditions) or split-belt treadmills with different left and right belt speeds (asymmetric conditions). We compare these experimental data with the results of mathematical modeling, in which simulated CPG circuits operate in similar symmetric and asymmetric conditions with matching or differing control drives to the left and right RGs. The obtained results support the proposed concept of state-dependent changes in RG operation and specific commissural interactions between the RGs. The performed simulations and mathematical analysis of model operation under different conditions provide new insights into CPG network organization and limb coordination during locomotion.
Excessive blood pressure variation is linked to development of hypertension and other diseases. This study assesses the relative role of respiratory sinus arrhythmia (RSA) and pulse pressure (PP) on the amplitude and timing of blood pressure variability with respiration (Traube-Hering (TH) Waves). We analyzed respiratory, electrocardiogram, and blood pressure traces from healthy, supine male subjects (n=10, mean age 26.7 ± 1.4) during 20-min epochs of resting, slow deep breathing (SDB), and recovery. Across all epochs, blood pressure and heart rate (HR) were modulated with respiration and the magnitude of RSA; TH waves increased during SDB. The data were deconstructed using a simple mathematical model of blood pressure to dissect the relative roles of RSA and PP on TH waves. We constructed the time series of the R-wave peaks and compared the recorded TH waves to that predicted by the model. Given that cardiac output is determined by both heart rate and stroke volume, it was surprising that the magnitude of the TH waves could be captured by only HR modulation. However, RSA alone did not accurately predict the timing of TH waves relative to the respiratory cycle. Adding respiratory modulation of PP to the model corrected the phase shift showing the expected pattern of BP rising during inspiration with the peak of the TH wave during early expiration. We conclude that short-term variability of blood pressure referred to as TH waves has at least two independent mechanisms whose interaction forms their pattern: RSA and respiratory-driven changes in PP.
In this study, we explore the functional role of striatal cholinergic interneurons, hereinafter referred to as tonically active neurons (TANs), via computational modeling; specifically, we investigate the mechanistic relationship between TAN activity and dopamine variations and how changes in this relationship affect reinforcement learning in the striatum. TANs pause their tonic firing activity after excitatory stimuli from thalamic and cortical neurons in response to a sensory event or reward information. During the pause striatal dopamine concentration excursions are observed. However, functional interactions between the TAN pause and striatal dopamine release are poorly understood. Here we propose a TAN activity-dopamine relationship model and demonstrate that the TAN pause is likely a time window to gate phasic dopamine release and dopamine variations reciprocally modulate the TAN pause duration. Furthermore, this model is integrated into our previously published model of reward-based motor adaptation to demonstrate how phasic dopamine release is gated by the TAN pause to deliver reward information for reinforcement learning in a timely manner. We also show how TAN-dopamine interactions are affected by striatal dopamine deficiency to produce poor performance of motor adaptation.
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