Translating striatal activity from brain slice to whole animal neurophysiology: A guide for neuroscience research integrating diverse levels of analysis

Abstract

An important goal of this review is highlighting research in neuroscience as examples of multilevel functional and anatomical analyses addressing basic science issues and applying results to the understanding of diverse disorders. The research of Dr. Michael Levine, a leader in neuroscience, exemplifies this approach by uncovering fundamental properties of basal ganglia function and translating these findings to clinical applications. The review focuses on neurophysiological research connecting results from in vitro and in vivo recordings. A second goal is to utilize these research connections to produce novel, accurate descriptions for corticostriatal processing involved in varied, complex functions. Medium spiny neurons in striatum act as integrators combining input with baseline activity creating motivational “events.” Basic research on corticostriatal synapses is described and links developed to issues with clinical relevance such as inhibitory gating, self‐injurious behavior, and relative reward valuation. Work is highlighted on dopamine–glutamate interactions. Individual medium spiny neurons express both D1 and D2 receptors and encode information in a bivalent manner depending upon the mix of receptors involved. Current work on neurophysiology of reward processing has taken advantage of these basic approaches at the cellular and molecular levels. Future directions in studying physiology of reward processing and action sequencing could profit by incorporating the divergent ways dopamine modulates incoming neurochemical signals. Primary investigators leading research teams should mirror Mike Levine's efforts in “climbing the mountain” of scientific inquiry by performing analyses at different levels of inquiry, integrating the findings, and building comprehensive answers to problems unsolvable without this bold approach.

Microfluidics for Neuronal Cell and Circuit Engineering

“…Given the complexity of neural circuits, mapping the anatomical and functional features of the brain remains a challenging task for neurobiologists. − From a clinical point of view, neuronal loss and dysfunction are both associated with a variety of neurological disorders. , Understanding the pathophysiology underlying such disorders at the cellular and circuit levels is key to developing novel and more effective therapeutic alternatives. Presently, the major approaches to understand brain function involve the use of native neural circuits within their environment in vivo, of brain slices ex vivo, and of in vivo–mimetic circuits assembled in vitro. − The latter enable to scale down the complexity of the in vivo system and to study circuit functionality under controlled experimental conditions. ,− However, conventional in vitro neuronal cultures on a flat substrate do not recapitulate the structure and organization of in vivo circuits and usually fail to mimic relevant microenvironmental cues. In this context, microfluidic devices constitute a powerful toolkit to engineer superior neuronal circuits that more closely resemble their in vivo counterparts. − …”