Striatal gating through up states and oscillations in the basal ganglia: Implications for Parkinson’s disease

► We propose a model for understanding up state physiology in striatal neurons and the pathophysiology of Parkinson’s disease. ► D2 and NMDA receptors regulate up states in striatal neurons projecting to the globus pallidus. ► In a low dopamine condition NMDA receptor activity increases and up states are of higher amplitude. ► This results in a strengthening of corticostriatal connections in the indirect basal ganglia pathway. ► In turn, the Strengthening of corticostriatal connections results in an abnormal representation of cortical rhythms in pallidal neurons. Up states are a hallmark of striatal physiology. Spontaneous activity in the thalamo-cortical network drives robust plateau depolarizations in the medium spiny projection neurons of the striatum. Medium spiny neuron firing is only possible during up states and is very tightly regulated by dopamine and NMDA receptors. In a rat model of Parkinson’s disease the medium spiny neurons projecting to the globus pallidus (indirect pathway) show more depolarized up states and increased firing. This is translated into abnormal patterns of synchronization between the globus pallidus and frontal cortex, which are believed to underlie the symptoms of Parkinson’s disease. Here we review our work in the field and propose a mechanism through which the lack of D2 receptor stimulation in the striatum allows the establishment of fixed routes of information flow in the cortico–striato-pallidal network.