Quantitative Estimate of Synaptic Inputs to Striatal Neurons during Up and Down StatesIn Vitro

Abstract

Up states are prolonged membrane potential depolarizations critical for synaptic integration and action potential generation in cortical and striatal neurons. They commonly result from numerous concurrent synaptic inputs, whereas neurons reside in a down state when synaptic inputs are few. By quantifying the composition, frequency, and amplitude of synaptic inputs for both states, we provide important constraints for state transitions in striatal network dynamics. Up and down states occur naturally in cortex-striatum-substantia nigra cocultures, which were used as an in vitro model in the present study. Spontaneous synaptic inputs during down states were extracted automatically in spiny projection neurons and fast spiking interneurons of the striatum using a newly developed computer algorithm. Consistent with a heterogeneous population of synaptic inputs, PSPs and PSCs showed no correlation in amplitude and rise time and occurred at relatively low frequencies of 10-40 Hz during the down state. The number of synaptic inputs during up states, estimated from the up-state charge and the unitary charge of down-state PSCs, was 217 +/- 44. Given the average up-state duration of 284 +/- 34 msec, synaptic input frequency was approximately 800 Hz during up-states for both neuronal types. Many down-state events reversed at the chloride reversal potential and were blocked by GABA(A) antagonists. The high correlation between up- and down-state reversal potential suggests that despite these drastic changes in synaptic input frequency, the ratio of inhibitory to excitatory currents is similar during both states.

D2Dopamine Receptors Colocalize Regulator of G-Protein Signaling 9-2 (RGS9-2) via the RGS9 DEP Domain, and RGS9 Knock-Out Mice Develop Dyskinesias Associated with Dopamine Pathways

“…Recordings were performed on these neurons, which were identified (Axioskop infrared differential interference contrast video microscopy; Zeiss, Jena, Germany) by their small size and irregular shape (densely arborizing recurrent axon collaterals). Medium spiny neurons have two electrophysiological states, a down state with resting membrane potentials below Ϫ80 mV and no spontaneous activity and an up state with resting membrane potentials above Ϫ80 mV and high-frequency spontaneous action potentials (10 -15 Hz) (Blackwell et al, 2003). In our experiments, Ͼ90% of the cells were in the down state.…”

Spike-Train Communities: Finding Groups of Similar Spike Trains

“…To look at cell assembly formation, I simulated 10 s of spontaneous activity within a 250 ϫ 250 ϫ 250 m cube of striatum, hence containing 1359 SPNs and 41 FSIs (Humphries et al, 2009b), driven by background cortical activity of ϳ500 spikes/s arriving at each neuron (Blackwell et al, 2003;Wolf et al, 2005;Humphries et al, 2009b). The algorithm was then applied to the spike trains of the 1344 SPNs that fired more than one spike during the simulation.…”

Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit

“…Synaptic input to the striatal FSIs predominantly activates GABAa or AMPA receptors (Blackwell et al, 2003), NMDA receptors are rare. The dendrodendritic gap junctions provide a further source of "synaptic" current (Koos & Tepper, 1999).…”

“…In a recent organotypic cortico-striatal-nigral co-culture study, Blackwell et al (2003) reported that a striatal MSN receives an average of around 800 synaptic events per second during its depolarised ("up") state, but they could not distinguish excitatory and inhibitory potentials. 2.…”