Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex during hyperdopaminergia ( approximately 500% of controls) with hyperkinesia, and after rapid and profound dopamine depletion (<0.2%) with akinesia in the same animal. Surprisingly, although most cortical and striatal neurons ( approximately 70%) changed firing rate during the transition between dopamine-related hyperkinesia and akinesia, the overall cortical firing rate remained unchanged. Conversely, neuronal oscillations and ensemble activity coordination within and between cortex and striatum did change rapidly between these periods. During hyperkinesia, corticostriatal activity became largely asynchronous, while during dopamine-depletion the synchronicity increased. Thus, dopamine-related disorders like Parkinson's disease may not stem from changes in the overall levels of cortical activity, but from dysfunctional activity coordination in corticostriatal circuits.

No abstract

Multielectrode arrays (MEAs) allow for acquisition of multisite electrophysiological activity with submillisecond temporal resolution from neural preparations. The signal to noise ratio from such arrays has recently been improved by substrate perforations that allow negative pressure to be applied to the tissue; however, such arrays are not optically transparent, limiting their potential to be combined with optical-based technologies. We present here multi-suction electrode arrays (MSEAs) in quartz that yield a substantial increase in the detected number of units and in signal to noise ratio from mouse cortico-hippocampal slices and mouse retina explants. This enables the visualization of stronger cross correlations between the firing rates of the various sources. Additionally, the MSEA's transparency allows us to record voltage sensitive dye activity from a leech ganglion with single neuron resolution using widefield microscopy simultaneously with the electrode array recordings. The combination of enhanced electrical signals and compatibility with optical-based technologies should make the MSEA a valuable tool for investigating neuronal circuits.