David T. Blake - US grants

discrimination learning; attention; neural plasticity; stimulus /response; brain electrical activity; sensorimotor system; time perception; behavioral /social science research tag; Aotus;

Cortical area 3b contains representations of the surfaces of the digits that are adjacent and non-overlapping in untrained owl monkeys. Recent work in the Merzenich laboratory has shown that simultaneous or alternating stimulation of the digits in a behavioral task causes the neural representations of these digits to merge or to segregate, respectively. In the proposed experiments we ask under what temporal and behavioral conditions will the neural representations of stimuli merge? Owl monkeys have been trained at tasks that present stimuli to adjacent distal fingerpads with near simultaneous stimulus timing. Awake behaving recordings will allow us to document the cortical changes that accompany changes in the animal's perceptual capabilities. The awake recordings will answer questions about the temporal and behavioral conditions under which single cortical neurons re-organize their spatial and temporal response properties.

DESCRIPTION (provided by applicant): This application outlines a direct study of the mechanisms of auditory learning. Animals are capable of making new associations between positive reinforcers, the sensory context that preceded them, and the motor acts that cause them. The proposed studies will use multiple microelectrode implant technology to record simultaneously from a large number of neurons in auditory cortex throughout a period in which an animal acquires a new association. The specific intent will be to observe how the auditory cortex representation of the sensory context is altered by the learning. The monkeys will be trained to discriminate short sound tones. As they begin to perform the task to receive rewards, their brain learning machinery is engaged and causes unavoidable changes in how sounds are represented. Data will be collected in parallel, in terms of the animal's perceptual capabilities and the response properties of neurons in auditory fields within and outside the behavioral tasks. The use of implants in neural systems has advanced much in the last decade; this study will apply that technology to study learning. In the first phase of training, animals will respond to short tones that are just higher in frequency than fixed comparison tones. Preliminary studies have shown that if the target stimulus comes from a fixed range, the representation of that frequency range grows and intensifies. After this initial phase, the animals will perform the same frequency discrimination task using randomized frequencies for comparison and target tone pips. A control experiment will replicate the trials of the first phase of training in naive animals that are only passive listeners. These studies should contribute to defining the plastic properties of cortical fields as dynamic learning neural networks. Such networks are most easily understood in terms of their initial sets of connections and their learning rules. This study will isolate and test different hypotheses for learning rules, and will lead to a greater understanding of the adaptive role of the cerebral cortex in general, both in instrumental learning and in classical conditioning.

[unreadable] DESCRIPTION (provided by applicant): The long-term objective of the application is a complete description and understanding of how the brain changes when a sensory discrimination is learned. The Principal Investigator has led recent technological advances that let cortical implants sample action potential responses from the same brain locations over many months. These advances provide the opportunity, for the first time, to study how the distributed generation of action potentials in the brain changes on a daily basis throughout the learning process. Our prior work has monitored animals throughout the learning process. In the first two days after selecting for targets and avoiding distractors, action potential responses to both task targets and non-targets increase several-fold, and receptive fields broaden spatially. With time, responsiveness returns to normal levels, and responses to task distractors become selectively suppressed. Our working hypothesis is that these plasticity effects depend only on cognitive reward associations. In the first study we will serially train implanted animals in detection and discrimination tasks in which the target assignment is kept constant, for several weeks at each task. This experiment will separate neuroplasticity effects that occur through associating rewards with task target stimuli and associating omission of reward with task distractors. Animals will then perform the same task with target and distractor assignments swapped, to reverse reward associations. Then, animals will be classically conditioned to the same stimuli, which preserve reward associations while introducing a broad range of behavioral changes; preliminary data shows minimal neuroplasticity results from this transition. Then, as a classical conditioning experiment, target and distractor reward associations will be reversed. Other studies will test coincident-input models of cortical plasticity against reward association models to determine which takes precedence when they are inconict. And lastly, studies will test hypotheses on how the neuroplasticity rules caused by these associations are implemented by the brain's neuromodulatory systems. Throughout each study, spike responses, local field potentials, and receptive fields in area 3b will be monitored before and during behavioral performance to create output measures to compare with behavioral data. [unreadable] [unreadable] This study proposes basic science investigations into circuitry underlying learning. It will lay the substrate for what is sure to be a very active area in public health in the coming decade. Abnormalities in these neuromodulatory centers, the Nucleus Basalis, Substantia Nigra, and Locus Coeruleus, are thought to be behind an array of neurological and mental disorders such as age-related cognitive decline, Alzheimer's disease, Parkinson's disease, Schizophrenia, General Depression, OCD, and addiction. Understanding how the brain changes when we learn will enable more targeted studies of how learning, and thus neuromodulatory activity, is abnormal in these neurological conditions. However, this is a basic science application, and so direct applicability to public health will depend upon follow-up applied studies. [unreadable] [unreadable] [unreadable]