Neurodevelopment and Plasticity in Social Neural Circuits

National Institute Of Mental Health

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Abstract

The developing visual brain is ever changing, incorporating rules for structural analyses, visually guided actions, and social meaning through childhood and 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 good 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. One recently published study from our group demonstrates that at least some portions of the visual brain are readily adaptable even in adulthood. Specifically, we recently reported the learning of single neurons related to high-level visual recognition memory in the ventral visual cortex of the brain (Koyano et al, 2023, Sci Adv). By tracking individual neurons across days and weeks, we found that the familiarity of objects impacts a population of neurons only gradually. Careful examination revealed that the division of labor in the neural population broke down by the rate of learning. Namely, some neurons showed signs of familiarity rather soon after new stimuli were introduced, within 2-3 days, whereas other neurons started to alter their responses much later, only after a few weeks. Within the population, this cascade of plasticity may link to the graded and continuous intensity of familiarity that accompanies exposure to stimuli. As more and more days elapsed, an increasing proportion of neurons in these face-related visual areas bore the mark of visual familiarity. This gradual accrual, and cell-specific time constant specialization, was completely unknown before the study and has important implications forunderstanding the process of visual learning. Early in life, the brain is even more adaptable. We are increasingly employing methods that allow us to track neural activity patterns over early life periods. This set of tools includes functional magnetic resonance imaging (fMRI), single-cell recordings, and optical recordings. We have focused much of this work on face patches, which are small, circumscribed regions of the temporal and prefrontal cortex showing greater fMRI responses to faces than to other categories of stimuli. The longitudinal nature of our studies allows us to investigate plasticity over multiple time scales. This research has been further aided by our development of an avatar face stimulus, whose animation, facial expressions, and environmental context is under complete experimental control. This stimulus toolbox has been of great use for systematically studying the factors that determine neural firing, for example in the context of the geometry of natural vision. However, 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 general approach has been central in preclinical research, and 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. In one ongoing project, we have been using local light stimulation to investigate electrophysiological and fMRI responses over time. The goal of this project is to understand the initial exuberance and gradual refinement of corticocortical circuits related to vision. In another study, we have been measuring cellular Ca++ fluorescence responses following the presentation of faces and other image stimuli. 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.