50 Years of Modeling Neural Activity: Celebrating Jack Cowans Career: Predicting responses to inhibitory synaptic input in substantia nigra pars reticulata neurons

摘要

The changes in firing probability produced by a synaptic input are usually visualized using the poststimulus time histogram (PSTH). It would be useful if postsynaptic firing patterns could be predicted from patterns of afferent synaptic activation, but attempts to predict the PSTH from synaptic potential waveforms using reasoning based on voltage trajectory and spike threshold have not been successful, especially for inhibitory inputs. We measured PSTHs for substantia nigra pars reticulata (SNr) neurons inhibited by optogenetic stimulation of striato-nigral inputs or by matching artificial inhibitory conductances applied by dynamic clamp. The PSTH was predicted by a model based on each SNr cell’s phase-resetting curve (PRC). Optogenetic activation of striato-nigral input or artificial synaptic inhibition produced a PSTH consisting of an initial depression of firing followed by oscillatory increases and decreases repeating at the SNr cell’s baseline firing rate. The phase resetting model produced PSTHs closely resembling the cell data, including the primary pause in firing and the oscillation. Key features of the PSTH, including the onset rate and duration of the initial inhibitory phase, and the subsequent increase in firing probability could be explained from the characteristic shape of the SNr cell’s PRC. The rate of damping of the late oscillation was explained by the influence of asynchronous phase perturbations producing firing rate jitter and wander. Our results demonstrate the utility of phase-resetting models as a general method for predicting firing in spontaneously active neurons and their value in interpretation of the striato-nigral PSTH.>NEW & NOTEWORTHY The coupling of patterned presynaptic input to sequences of postsynaptic firing is a Gordian knot, complicated by the multidimensionality of neuronal state and the diversity of potential initial states. Even so, it is fundamental for even the simplest understanding of network dynamics. We show that a simple phase-resetting model constructed from experimental measurements can explain and predict the sequence of spike rate changes following synaptic inhibition of an oscillating basal ganglia output neuron.