Information processing in the nucleus accumbens: In vivo electrophysiological studies

The nucleus accumbens (NAcc) is a brain region where prefrontal cortex (PFC) and limbic afferents, especially those from the hippocampus and basolateral amygdala (BLA), converge. In addition to limbic and PFC efferents, the NAcc receives mesolimbic dopamine (DA) projections from the ventral tegmental area (VTA) that are crucial for reward seeking behavior.; The first aim of the studies in the thesis is to understand the mechanisms of PFC and limbic information integration and output selection in the NAcc based on NAcc neuron membrane potential states and timing of limbic and cortical synaptic input arrivals. The second aim of the studies is to unveil a possible involvement of mesolimbic DA abnormality in the NAcc in the pathophysiology of schizophrenia using an animal model.; In chapter I, background information about the anatomy and function of the NAcc and implication of its dysfunction in schizophrenia is briefly described.; In chapter II, synchronous activity between the NAcc and hippocampus or the NAcc and PFC is presented. The results in chapter II indicate that, if synchronous inputs from a population of hippocampal neurons affect neural activity in the NAcc, membrane potential fluctuations among a population of NAcc neurons are also synchronized. In chapter III, this hypothesis was tested by simultaneous in vivo intracellular and extracellular UP recordings in the NAcc.; In chapter IV, PFC and limbic synaptic integration in NAcc neurons were directly examined by paired electrical stimulation in the PFC and limbic structures with in vivo intracellular recordings in NAcc neurons. Simultaneous stimulation of the PFC and limbic structures evoked more stable synaptic responses in NAcc neurons than responses evoked by stimulation of PFC or limbic structures alone, suggesting that synchronous arrivals of PFC and limbic inputs enhance information encoding in the NAcc. Chapters V and VI present the experiments conducted in an animal model of schizophrenia, in which animals receive a neonatal VH lesion. In chapter VI, in order to investigate the mechanisms of altered NAcc responses to VTA activation, the effects of an adult PFC lesion on these responses were examined in animals with a neonatal VH lesion.; In chapter VII, experiments investigating induction of long term potentiation (LTP) in the entorhinal cortex (ENT)-PFC pathway are described. In chapter VIII, implications from the results of experiments presented in chapters II--VII are discussed. Limbic and cortical synaptic integration and the role of mesolimbic DA in NAcc neural ensemble information processing are discussed in relation to set shifting, an important cognitive function essential for goal-directed behavior. (Abstract shortened by UMI.)...