Schizophrenia, Parkinson's disease, Tourette's syndrome, obsessive-compulsive disorder and drug addiction, are only some of the relevant clinical conditions that have been related to dysfunction of brain dopamine systems and abnormal processing of cortical input in the striatum. The robust membrane potential depolarizations (""""""""up states"""""""") during which striatal neurons become responsive to the fine structure of cortical input, are synaptically-driven events invoked by the cortex itself and probably shaped by dopamine-regulated membrane currents. The suggestion that the striatum behaves as an """"""""action selection"""""""" network, raised interest in understanding how dynamic patterns of cortical activity are represented in the striatum and how this representation is modified by changes in dopamine neurotransmission. By simultaneously recording the population activity of cortical neurons and the membrane potential of striatal neurons, we have recently clarified some aspects of the temporal dynamics of up states. In this proposal, we plan to analyze the representation of spatial variations of cortical activity on striatal neurons by recording field potentials and multiunit activity from multiple cortical sites together with the membrane potential of striatal neurons in anesthetized rats. Our main goal is to understand how spatially-distributed and dynamically-changing patterns of cortical activity are reflected in the membrane potential (as an index of synaptic input) and firing pattern (as an index of neuronal output) of striatal neurons. Furthermore, we will investigate the impact of cortical activity on striatal neurons in genetically-modified mice lacking functional D1 or D2 dopamine receptors. This research will be done primarily in Argentina, at the Buenos Aires University School of Medicine, in collaboration with M. Gustavo Murer, as an extension of NIH grant # R01MH060131.
| Galiñanes, Gregorio L; Taravini, Irene R E; Murer, M Gustavo (2009) Dopamine-dependent periadolescent maturation of corticostriatal functional connectivity in mouse. J Neurosci 29:2496-509 |
| Kasanetz, Fernando; Riquelme, Luis A; Della-Maggiore, Valeria et al. (2008) Functional integration across a gradient of corticostriatal channels controls UP state transitions in the dorsal striatum. Proc Natl Acad Sci U S A 105:8124-9 |
| Kasanetz, Fernando; Riquelme, Luis A; O'Donnell, Patricio et al. (2006) Turning off cortical ensembles stops striatal Up states and elicits phase perturbations in cortical and striatal slow oscillations in rat in vivo. J Physiol 577:97-113 |
