UCSF

Neural computation can occur at multiple spatial and temporal timescales. The sum total of all of these processes is to guide optimal behaviors within the context of the constraints imposed by the physical world. How the circuits of the brain achieves this goal represents a central question in systems neuroscience. Here I explore the many ways in which the circuits of the brain can process information at both the micro and meso scale. Understanding the way information is represented and processed in the brain could shed light on the neuropathology underlying complex neuropsychiatric diseases such as autism and schizophrenia. Chapter 2 establishes an experimental paradigm for assaying patterns of microcircuit activity and examines the role of dopaminergic modulation on prefrontal microcircuits. We find that dopamine type 2 (D2) receptor activation results in an increase in spontaneous activity while dopamine type 1 (D1) activation does not. Chapter 3 of this dissertation presents a study that illustrates how cholingergic activation normally produces what has been suggested as a neural substrate of attention; pairwise decorrelation in microcircuit activity. This study also shows that in two etiologicall distinct mouse models of autism, FMR1 knockout mice and Valproic Acid exposed mice, this ability to decorrelate in the presence of cholinergic activation is lost. This represents a putative microcircuit level biomarker of autism. Chapter 4 examines the structure/function relationship withing the prefrontal microcircuit. Spontaneous activity in prefrontal microcircuits is shown to be organized according to a small world architecture. Interestingly, this architecture is important for one concrete function of neuronal microcircuits; the ability to produce temporally stereotyped patterns of activation. In the final chapter, we identify subnetworks in chronic intracranial electrocorticographic (ECoG) recordings using pairwise electrode coherence and dimensionality reduction techniques. We show that we can further reduce the dimensionality of these networks by identifying 'key-interactions' that are informative of the overall subnetwork state at any given point in time. This study highlights that redundancy in ECoG data can be exploited to identify low-dimensional representation of brain-wide subnetworks. Taken together, these studies represent the development of multiple technological and analytical techniques aimed at understanding how information is processed and modulated at emergent circuit and network levels as well as understanding their dysfunction in a neuropsychiatric disease state.