NEURAL DYNAMICS IN CORTEX-STRIATUM COCULTURES .2. SPATIOTEMPORAL CHARACTERISTICS OF NEURONAL-ACTIVITY

Neural dynamics in organotypic cortex-striatum co-cultures grown for t hree to six weeks under conditions of dopamine deficiency are describe d. Single neuron activities were recorded intra- and extracellularly, and spatiotemporal spreading of population activity was mapped using v oltage-sensitive dyes. The temporal properties of spike firing were ch aracterized by interspike interval histograms, autocorrelation and cro sscorrelation. Cortical pyramidal neurons (n = 40) showed irregular fi ring with a weak tendency to burst or to oscillate. Crosscorrelations revealed strong near-coincident firing and synaptic interactions. Disi nhibition was a notable feature in a strongly firing cortical interneu ron. Cortical activity spread in the co-culture, thus inducing an over all, homogeneous depolarization in the striatal part. Striatal cells w ere divided into principal cells and type I and II secondary cells. Pr incipal cells (n = 40) were similar to those reported previously in vi vo. Spiking activity ranged from irregular spiking at very low rates t o episodic bursting, with an average burst duration of 1 s. Interspike intervals were single-peaked. Intracellular recordings revealed chara cteristic, long-lasting subthreshold depolarizations (''enabled state' ') that were shortened by local muscarinic receptor blockade. During p rolonged time periods in the ''enabled state'', locally applied bicucu lline induced strong firing in most principal neurons. Striatal second ary type I neurons (n = 25) showed high spiking rates, single- and dou ble-peaked interval histograms and low-threshold, short-lasting stereo typed bursting activity and occasional rhythmic bursting. The firing o f these neurons was increased by bicuculline. Crosscorrelations showed synchronization of these cells with principal cell activity. Secondar y type II neurons (n = 15) revealed tonic, irregular firing patterns s imilar to cortical neurons, except with occasional firing in doublet s pikes. We conclude that under conditions of dopamine deficiency in cor ticostriatal co-cultures (i) the cortex induces the ''enabled'' stale and typical bursting mode in striatal principal neurons; (ii) principa l neurons are strongly inhibited during the ''enabled'' state; (iii) m uscarinic activity, presumably from tonically active striatal choliner gic interneurons, stabilizes the ''enabled'' state; (iv) striatal GABA ergic interneurons receive synaptic inhibition and take part in synchr onized activity among striatal principal cells. Our results favor the view of the striatum as a lateral inhibition network.