Neurodevelopment and Plasticity in Social Neural Circuits

National Institute Of Mental Health

Investigators

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Abstract

We have applied a multifaceted approach to study the operation and development of circuits supporting social vision in the cerebral cortex. The developing visual brain continually incorporates information to support the analyses of faces and gestures, visually guided actions, and social meaning. This process begins at birth and advances in a “coarse to fine” manner from childhood into adulthood, with the refinement of social perception continuing well into adulthood. The core operations of social perception, memory, abstraction, and behavior depend upon this slow and integrative process, which is inbuilt into brain development. Importantly, the long period of experience-based modification means that the brains of individuals differ in their capacities and, to some extent, in their organization and physiology. In the case of brain damage and diseases, the differences in the brain translate directly to changes in abilities. For example, damage to very specific parts of the temporal lobe can lead to the inability to recognize individual faces while not affecting the recognition of other objects. Damage in other areas can leave subjects with a difficulty in recognizing facial expression, voice intonation, or even prompt them to believe that their spouse is an impostor. Similarly, abnormal development of the circuits in psychiatric diseases, for example those spurring social interaction, can lead to debilitating perceptual deficits in understanding social information. Researchers do not have a clear idea of how this specialization comes about and is refined over time, even though it was nearly 50 years ago that researchers discovered that the visual brain has specific areas dedicated for social information. Over the past decade, our group has studied multiple aspects of visual social processing, with many studies focused on the brain learns and encodes facial structure to support individual recognition. An important principle arising from this research (reviewed in Leopold, Curr Opinions in Neurobiol, 2024) is that single neurons carry information representing a superposition of multiple different signals, particularly during natural modes of visual interaction. This mixing of signals, which is much less obvious during the traditional brief presentation of isolated stimuli, incorporates everyday elements of vision, such as spatial and temporal context, which are crucial for navigating social situations. Beyond describing the operational principles of specialized cortical areas, our program asks how the brain learns from its experiences. We have approached this in traditional ways, through the repeated exposure of stimuli, as well as through the development of novel methods. Specifically, to gain sufficient traction on the biology of neural plasticity during early life, it has been important to develop and apply new tools that allow for the brain-wide delivery of viral products. This approach allows for the application of genetic and pharmacological methods to test or reversibly perturb structures involved in social perception. Related approaches have been may ultimately have clinical applications, such as for the application of gene therapy. We have been applying this method with the context of basic neuroscience in order to evaluate the processes by which developing brains gradually specialize. Our preliminary findings from this project indicate that mid-gestational viral delivery into the cerebroventricular system can lead to the widespread expression of transgenes, particularly in the cerebral cortex. In one ongoing project, we have been using this method to express light-sensitive opsins in neurons. Then, using light stimulation to stimulate neurons, we are able to investigate electrophysiological and fMRI responses across the brain. While this project is in its formative stages, the long-term goal of this project is to apply this combinatorial approach throughout development to understand the initial exuberance and gradual refinement of corticocortical circuits related to vision. Another offshoot of this approach utilizes the expression of Ca++ fluorescence probes in cortical cells for the purposes of optical imaging of activity. Similar to the microelectrode recordings, these recordings also permit longitudinal tracking over weeks and months. The present study aims to understand the nature of cellular selectivity, as well as the similarity of preference among neighboring neurons. In the future, our Ca++ fluorescence work will also be used to investigate whether neurons in face selective areas modify their response profiles during development, for example as the subject learns new individuals or environmental contexts.