Our research interests:
The electrophysiology of prefrontal cortical and ventral striatal brain circuits. The physiological role of dopamine in these brain regions Maturation of these circuits during adolescence The neural bases of schizophrenia and related disorders The physiological mechanisms involved in comorbidity for schizophrenia and drug addiction

Schizophrenia is a devastating disorder in which the nature of changes occurring in the brain remains unclear. Extensive research has shown that a number of brain regions and systems are involved in schizophrenia or in its treatment; these include the prefrontal cortex, temporal lobe (hippocampus), ventral striatum and dopamine systems. Our research is directed to understanding the neurobiology of schizophrenia and related neuropsychiatric disorders focusing on the interactions among these systems. The primary approach involves the use of electrophysiological techniques, looking particularly at the modulation of information flow through the neural circuits linking these brain regions. Both in vivo and in vitro intracellular recordings from neurons in the prefrontal cortex and nucleus accumbens are employed to study these interactions. We are focusing on the role of dopamine on the control of such information flow through the ventral basal ganglia circuit with experiments involving stimulation of the source (the ventral tegmental area, or VTA) and application of agonists/antagonists. We have shown that neurons in the prefrontal cortex and ventral striatum alternate between active and inactive states, as defined by changes in their membrane potential. The hippocampus and other limbic inputs may gate prefrontal cortical throughput in the ventral striatum by enabling active states; this phenomenon is also controlled by dopamine, a transmitter implicated in schizophrenia.

We are studying these interactions in developmental animal models of schizophrenia. A neonatal hippocampal lesion produces behavioral alteration that resemble phenomena observed in schizophrenia, which emerge after puberty. A number of electrophysiological changes, primarily in the response of the ventral basal ganglia circuit to activation of the mesolimbic projections, have been observed. We are also performing many of these studies combining electrophysiology with electrochemical detection of dopamine release. Our goal is to understand the function and interactions among systems involved in higher cognitive functions, that are known to be disturbed in a number of neuropsychiatric disorders. We are also collaborating with colleagues that provide us with genetic models of the disease, such as DISC1 or variations in COMT.

We are also interested in exploring the changes in these circuits and the functions they subserve during adolescence. We have recently shown that inhibitory interneurons in the prefrontal cortex change dramatically their response to dopamine during adolescence, a finding that highlights the complex maturation of these circuits, so important for decision making, during that late developmental stage. We are exploring the mechanisms behind such maturation, and whether and how they become affected in schizophrenia models.

Another set of experiments are aimed at elucidating whether the increase liability for drug taking is indeed a self-medicating attempt. Rats with a neonatal ventral hippocampal lesion self-administer stimulants more readily than their control littermates. We are exploring whether this is due to altered synaptic activity and dopamine responses within the prefrontal cortex, and whether this is another symptom of the condition.