Biomedical subjects

Genela Morris

Publications and source records attributed to Genela Morris.

7 recordsLinked to original sources

PubMed2006

Midbrain dopamine neurons encode decisions for future action.

Current models of the basal ganglia and dopamine neurons emphasize their role in reinforcement learning. However, the role of dopamine neurons in decision making is still unclear. We recorded from dopamine neurons in monkeys engaged in two types of trial: reference trials in an instructed-choice task and decision trials in a two-armed bandit decision task. We show that the activity of dopamine neurons in the decision setting is modulated according to the value of the upcoming action. Moreover, analysis of the probability matching strategy in the decision trials revealed that the dopamine population activity and not the reward during reference trials determines choice behavior. Because dopamine neurons do not have spatial or motor properties, we conclude that immediate decisions are likely to be generated elsewhere and conveyed to the dopamine neurons, which play a role in shaping long-term decision policy through dynamic modulation of the efficacy of basal ganglia synapses.

Animals↗

PubMed2005

Physiological studies of information processing in the normal and Parkinsonian basal ganglia: pallidal activity in Go/No-Go task and following MPTP treatment.

Understanding the role of the basal ganglia in day to day behavior is critical for a better understanding of the role of these structures in pathological states--such as Parkinson's disease. To elucidate this connection, we studied pallidal activity in a monkey performing a delayed release Go/No-Go task and in monkeys treated with the dopaminergic neurotoxin--MPTP. We compared the results with the predictions of the action selection and reinforcement driven dimensionality reduction models of the basal ganglia. The fraction of responding pallidal neurons, as well as the ratio of positive to negative responses, were equal in the Go and the No-Go modes. The fraction of pallidal neurons with significant responses following the trigger signal (19/26) was higher than that following the visual cue (11/26); however, the fraction of negative responses was significantly higher following the cue signal (47%) than that following the trigger signal (22%). Most (80%) of the cue responses were sensitive to the laterality of the cue, whereas only 25% of the responses following the trigger signal were sensitive to the cue or movement direction. Finally, pallidal spiking activity was not correlated in the normal behaving monkey, and became highly synchronized following MPTP treatment. We conclude that pallidal activity in the normal monkey is consistent with the model of action selection, assuming that action is selected following the visual cue. However, the reinforcement driven dimensionality reduction model is consistent with both the Go/No-Go responses and the normal/MPTP correlation studies.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2004

Independent coding of movement direction and reward prediction by single pallidal neurons.

Associating action with its reward value is a basic ability needed by adaptive organisms and requires the convergence of limbic, motor, and associative information. To chart the basal ganglia (BG) involvement in this association, we recorded the activity of 61 well isolated neurons in the external segment of the globus pallidus (GPe) of two monkeys performing a probabilistic visuomotor task. Our results indicate that most (96%) neurons responded to multiple phases of the task. The activity of many (34%) pallidal neurons was modulated solely by direction of movement, and the activity of only a few (3%) pallidal neurons was modulated exclusively by reward prediction. However, the activity of a large number (41%) of single pallidal neurons was comodulated by both expected trial outcome and direction of arm movement. The information carried by the neuronal activity of single pallidal neurons dynamically changed as the trial progressed. The activity was predominantly modulated by both outcome prediction and future movement direction at the beginning of trials and became modulated mainly by movement-direction toward the end of trials. GPe neurons can either increase or decrease their discharge rate in response to predicted future reward. The effects of movement-direction and reward probability on neural activity are linearly summed and thus reflect two independent modulations of pallidal activity. We propose that GPe neurons are uniquely suited for independent processing of a multitude of parameters. This is enabled by the funnel-structure characteristic of the BG architecture, as well as by the anatomical and physiological properties of GPe neurons.

Action Potentials↗

PubMed2004

Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons.

Midbrain dopamine and striatal tonically active neurons (TANs, presumed acetylcholine interneurons) signal behavioral significance of environmental events. Since striatal dopamine and acetylcholine affect plasticity of cortico-striatal transmission and are both crucial to learning, they may serve as teachers in the basal ganglia circuits. We recorded from both neuronal populations in monkeys performing a probabilistic instrumental conditioning task. Both neuronal types respond robustly to reward-related events. Although different events yielded responses with different latencies, the responses of the two populations coincided, indicating integration at the target level. Yet, while the dopamine neurons' response reflects mismatch between expectation and outcome in the positive domain, the TANs are invariant to reward predictability. Finally, TAN pairs are synchronized, compared to a minority of dopamine neuron pairs. We conclude that the striatal cholinergic and dopaminergic systems carry distinct messages by different means, which can be integrated differently to shape the basal ganglia responses to reward-related events.

Acetylcholine↗

PubMed2004

Discharge rate of substantia nigra pars reticulata neurons is reduced in non-parkinsonian monkeys with apomorphine-induced orofacial dyskinesia.

Involuntary movements (dyskinesia) are a common symptom of dopamine-replacement therapy in parkinsonian patients, neuroleptic drug treatment of mental patients, and tic disorders. Levodopa-induced dyskinesia has been shown to be associated with substantial reduction of firing rate in the internal part of the globus pallidus. This study characterizes the changes that occur in the activity of the substantia nigra pars reticulata (SNr) of non-parkinsonian (normal) monkeys with apomorphine (APO)-induced orofacial dyskinesia. We conducted extracellular recordings of SNr neurons of two monkeys before and after induction of orofacial dyskinesia by systemic administration of APO. Involuntary orofacial movements appeared a few minutes after the injections and lasted 20-40 min. Almost all recorded neurons changed their firing rate after APO injection (96%), and most declined (70%). The mean amplitude of decreases was also larger than that of increases (40 vs. 21% of the control rate). Changes in firing pattern were not significant on average. Pairs of SNr neurons were uncorrelated before APO injection, similar to the normal pallidum. However, unlike the increased correlations in the pallidum that accompany parkinsonism, orofacilal dyskinesia in non-parkinsonian monkeys was not associated with changes in correlation between SNr neurons. We conclude that normal monkeys treated with APO can model orofacial dyskinesia and tic disorders that are a consequence of dopaminergic over-activity. These symptoms appear to be more related to reduced firing rate of SNr neurons and thus to disinhibition of their targets, than to changes in pattern and synchronization.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2003

Information processing, dimensionality reduction and reinforcement learning in the basal ganglia.

Modeling of the basal ganglia has played a major role in our understanding of this elusive group of nuclei. Models of the basal ganglia have undergone evolutionary and revolutionary changes over the last 20 years, as new research in the fields of anatomy, physiology and biochemistry of these nuclei has yielded new information. Early models dealt with a single pathway through the nuclei and focused on the nature of the processing performed within it, convergence of information versus parallel processing of information. Later, the Albin-DeLong "box-and-arrow" model characterized the inter-nuclei interaction as multiple pathways while maintaining a simplistic scalar representation of the nuclei themselves. This model made a breakthrough by providing key insights into the behavior of these nuclei in hypo- and hyper-kinetic movement disorders. The next generation of models elaborated the intra-nuclei interactions and focused on the role of the basal ganglia in action selection and sequence generation which form the most current consensus regarding basal ganglia function in both normal and pathological conditions. However, new findings challenge these models and point to a different neural network approach to information processing in the basal ganglia. Here, we take an in-depth look at the reinforcement driven dimensionality reduction (RDDR) model which postulates that the basal ganglia compress cortical information according to a reinforcement signal using optimal extraction methods. The model provides new insights and experimental predictions on the computational capacity of the basal ganglia and their role in health and disease.

Animals↗

PubMedDate not supplied

Anatomical funneling, sparse connectivity and redundancy reduction in the neural networks of the basal ganglia.

The major anatomical characteristics of the main axis of the basal ganglia are: (1) Numerical reduction in the number of neurons across layers of the feed-forward network, (2) lateral inhibitory connections within the layers, and (3) neuro-modulatory effects of dopamine and acetylcholine, both on the basal ganglia neurons and on the efficacy of information transmission along the basal ganglia axis. We recorded the simultaneous activity of neurons in the output stages of the basal ganglia as well as the activity of dopaminergic and cholinergic neurons during the performance of a probability decision-making task. We found that the functional messages of the cholinergic and dopaminergic neurons differ, and that the cholinergic message is less specific than that of the dopaminergic neurons. The output stage of the basal ganglia showed uncorrelated neuronal activity. We conclude that despite the huge numerical reduction from the cortex to the output nuclei of the basal ganglia, the activity of these nuclei represents an optimally compressed (uncorrelated) version of distinctive features of cortical information.

Animals↗