||J. Wayne Aldridge
Statement on Research
My overarching research goal is to understand how the brain controls behavior. I have a particular focus on information processing in neurons and neuronal circuits in the basal ganglia related to reward and movement. As a behavioral neuroscientist, I use a combination of tools, experimental psychology and electrophysiology, to explore functional neural mechanisms. To this end, my experiments are designed to study the pattern and timing of neural activity in relation to the presentation of rewards and cues that predict rewards, and to learned and instinctive movements. The principal method I use is to record electrical activity of individual nerve cells while animals behave freely and respond to learned sensory cues. Experimental manipulations include: Pavlovian and instrumental training, diminished or boosted motivational drive states (e.g., diuretic salt depletion), mesolimbic activation (via sensitization and acute injections), and pharmacological stimulation (via systemic and intracranial injections of neurotransmitter agonists and antagonists). My research has clinical relevance to understanding drug addiction and neurological syndromes such as Parkinson’s disease, Huntington’s disease, Tourette syndrome and other disorders related to basal ganglia dysfunction. It has been funded by NIH including National Institute on Drug Abuse (NIDA) and the National Institutes on National Institute of Neurological Disorders and Stroke (NINDS). I also have received support from private foundations (e.g., Tourette Syndrome Association).
My current, central focus is to study neural correlates of motivational behavior. My aim is to understand spike discharge parameters in individual neurons and assemblies of neurons that code the incentive and hedonic properties of rewards. My students, colleagues and I have shown that in the ventral pallidum, a key output structure of the ventral/limbic portion of the basal ganglia, neural activity encodes information about reward. We demonstrated that mesolimbic activation shifts neural coding of motivational conditioned stimuli in the ventral pallidum from a mode that was responsive to predictive cues toward a mode dominated by responses to cues that represent incentive motivational value. This shift suggests one possible mechanism on how incentive cues might trigger relapse in human addicts and “pull” individuals toward drug rewards. Besides incentive value, we have shown in recent work that neurons in the ventral pallidum also encode the hedonic value of rewards. Furthermore, neural activity in the ventral pallidum tracks the current motivational value of cues dynamically and will follow changes in the cues dependent on the physiological appetitive state that is relevant to reward.
In an effort to probe the details of neuronal coding mechanisms and determine the ‘computational logic’ of nerve cells as elements in assemblies of neurons, we strive to achieve a fine-grained analysis of timing and patterns of neuronal activity in relation to behavior. We evaluate the frequency of spike activity, bursting patterns of spikes, recruitment properties across neurons, interaction between neurons, and response profile, etc. We have evidence that neurons in the basal ganglia may use both rate and population codes to represent behavior. The interaction of neurons is modulated dynamically from moment to moment at very short time scales (seconds) across behavior. In other words, activity profiles of neuronal circuits are in a continual state of flux that depends on behavior. This is a challenge to our analyses and highlights the critical role of behavior correlates in characterizing neural mechanisms. In recent work, as one example, we have shown that ventral pallidal neurons are responsive to multiple behavioral events. These multiple responses represent a signature pattern for a neuron that we have characterized as a “profile” of activation. Most importantly, we demonstrated that the population of neural profiles changes to reflect levels of mesolimbic activation. These computational details evident at this cellular level of analysis demonstrate the importance of a balanced analysis considering both behavioral events and neurophysiological properties to understand neural mechanisms of behavior. The basal ganglia are particularly interesting structures of the brain as they integrate sensory, motor and affective information from the cortex and other brain regions.
Neural Mechanisms of Movement:
Our experiments suggest that neurons in the neostriatum and substantia nigra reticulata represent a neural code for the implementation of natural action pattern sequences. Thus, the basal ganglia may play a key role in implementing grooming syntax and warm-up (transition from resting to walking) movement sequences and it is consistent with the idea that the basal ganglia in humans may be a repository for nondeclarative memories or motor habits and may play a role in the automatic execution of well-learned motor behavior. In our animal model we have also demonstrated that grooming sequences are under dopaminergic control; specifically, D1 agonists enhance and D2 agonists diminish sequence behavior. Thus, rodent grooming behavior and other natural behavioral patterns provide useful model systems to study the organization and neuronal mechanisms of sequential behavior. We can compare neural coding in stereotyped, syntactical sequences with movements in flexible, less rigidly structured patterns. A better understanding of the neural and pharmacological mechanisms related to sequence control might lead to new therapeutic tactics for neurological treatments.
Although my experiments have focused on the basal ganglia as a model system, the findings apply to other regions of the brain as well. I look forward to collaborations where other questions might be asked and other brain regions explored. Currently I have consulting and experimental collaborations with several faculty members in several departments at the University of Michigan. My collaboration with Dr. Kent Berridge remains fruitful and satisfying. Our most recent work on ventral basal ganglia mechanisms related to reward has been well-received and productive. In a new study, I am collaborating with Dr. Terry Robinson to explore the neural correlates of ‘sign tracking’ and ‘goal tracking’ in the ventral pallidum and nucleus accumbens. The properties of the ventral pallidum suggest that it is a key integrative structure for the representation of reward in brain circuits. Our findings are exciting and indicate that experimental trail should be productive for some years to come.