[Functional analysis of the roles of direct and indirect pathways by using immunotoxin-mediated cell targeting approach]

Abstract

The neural circuit connecting the cerebral cortex and the basal ganglia mediates a variety of brain functions including voluntary movement, motor learning, and reinforcement learning. These functions are dependent on midbrain dopamine systems that innervate the prefrontal cortex and the striatum. The pathogenesis of certain neurological and neuropsychiatric diseases involves the dysfunction of these dopamin systems; some of these diseases include Parkinson's disease, schizophrenia, and attention deficit hyperactivity disorder. To understand the physiology and pathology of brain functions, the mechanisms of neural circuitry that controls behaviors should be studied. Immunotoxin-mediated cell targeting is an approach employed in transgenic animals to eliminated specific neuronal types from a neuronal circuitry. This approach has been used to study the neural circuit mechanism in the central and peripheral nervous systems. Here, we describe the use of immunotoxin-mediated cell targeting for studying the neural circuitry that underlies the motor behavior demonstrated in response to systemic dopamine stimulation; further, we propose the potential mechanism that controls direct and indirect striatal pathway-dependent behavior.