Firing rate and pattern heterogeneity in the globus pallidus arise from a single neuronal population

Abstract

Deister CA, Dodla R, Barraza D, Kita H, Wilson CJ. Firing rate and pattern heterogeneity in the globus pallidus arise from a single neuronal population. J Neurophysiol 109: 497-506, 2013. First published October 31, 2012 doi:10.1152/jn.00677.2012.-Intrinsic heterogeneity in networks of interconnected cells has profound effects on synchrony and spike-time reliability of network responses. Projection neurons of the globus pallidus (GPe) are interconnected by GABAergic inhibitory synapses and in vivo fire continuously but display significant rate and firing pattern heterogeneity. Despite being deprived of most of their synaptic inputs, GPe neurons in slices also fire continuously and vary greatly in their firing rate (1-70 spikes/s) and in regularity of their firing. We asked if this rate and pattern heterogeneity arises from separate cell types differing in rate, local synaptic interconnections, or variability of intrinsic properties. We recorded the resting discharge of GPe neurons using extracellular methods both in vivo and in vitro. Spike-to-spike variability (jitter) was measured as the standard deviation of interspike intervals. Firing rate and jitter covaried continuously, with slow firing being associated with higher variability than faster firing, as would be expected from heterogeneity arising from a single physiologically distinct cell type. The relationship between rate and jitter was unaffected by blockade of GABA and glutamate receptors. When the firing rate of individual neurons was altered with constant current, jitter changed to maintain the rate-jitter relationship seen across neurons. Long duration (30 -60 min) recordings showed slow and spontaneous bidirectional drift in rate similar to the acrosscell heterogeneity. Paired recordings in vivo and in vitro showed that individual cells wandered in rate independently of each other. Input conductance and rate wandered together, in a manner suggestive that both were due to fluctuations of an inward current.

Stochastic slowly adapting ionic currents may provide a decorrelation mechanism for neural oscillators by causing wander in the intrinsic period

“…Evidence exists for the contribution of intrinsic mechanisms to variability in the cycle-to-cycle period in spontaneously active vertebrate neurons. Long-term (minute to hours) trends in the spontaneous spike rate have been observed in neurons in the external segment of the globus pallidus (GPe) in anesthetized rats and brain slice preparations (Deister et al 2012). These long-term fluctuations are distinguished from cycle-to-cycle jitter in the interspike interval (ISI) by calling the slow fluctuations "wander" in the period.…”

“…These long-term fluctuations are distinguished from cycle-to-cycle jitter in the interspike interval (ISI) by calling the slow fluctuations "wander" in the period. Elegant experiments (Deister et al 2012) using paired recordings of multiple neurons revealed that the spike rates of each cell wandered independently. This experimental design eliminates temperature or other variables that the cells have in common as the source of the wander.…”

Do gap junctions regulate synchrony in the Parkinsonian basal ganglia?

“…Since neurons firing at widely different rates do not tend to synchronize with each other, this cellular heterogeneity may make the GPe less susceptible to synchronized inputs. Deister et al [2013] therefore describe a powerful mechanism of decorrelation in the healthy GPe. However, changes in this heterogeneity after dopamine depletion have not yet been investigated.…”

“…In contrast, studies using healthy rat brain slices described three electrophysiological subgroups of neurons in the GP Stanford, 2000, Bugaysen et al, 2010]. However, other in vitro studies reported no clear qualitative electrophysiological differences amongst GP neurons and challenge the existence of distinct GP neuron types [Chan et al, 2004, Hashimoto and Kita, 2006, Günay et al, 2008, Chan et al, 2011, Deister et al, 2013.…”

“…Recently, Deister et al [2013] suggested cellular heterogeneity as an active decorrelation mechanism. They found that the heterogeneity in firing rates and patterns found in GP neurons in healthy rats are not due to multiple cell types or synaptic transmission but rather caused by a change over time in cellular properties common to all neurons, leading to different cellular characteristics within minutes.…”