T-type calcium channels promote predictive homeostasis of input-output relations in thalamocortical neurons of lateral geniculate nucleus

Abstract

A general theory views the function of all neurons as prediction, and one component of this theory is that of “predictive homeostasis” or “prediction error.” It is well established that sensory systems adapt so that neuronal output maintains sensitivity to sensory input, in accord with information theory. Predictive homeostasis applies the same principle at the cellular level, where the challenge is to maintain membrane excitability at the optimal homeostatic level so that spike generation is maximally sensitive to small gradations in synaptic drive. Negative feedback is a hallmark of homeostatic mechanisms, as exemplified by depolarization-activated potassium channels. In contrast, T-type calcium channels exhibit positive feedback that appears at odds with the theory. In thalamocortical neurons of lateral geniculate nucleus (LGN), T-type channels are capable of causing bursts of spikes with an all-or-none character in response to excitation from a hyperpolarized potential. This “burst mode” would partially uncouple visual input from spike output and reduce the information spikes convey about gradations in visual input. However, past observations of T-type-driven bursts may have resulted from unnaturally high membrane excitability. Here we have mimicked within rat brain slices the patterns of synaptic conductance that occur naturally during vision. In support of the theory of predictive homeostasis, we found that T-type channels restored excitability toward its homeostatic level during periods of hyperpolarization. Thus, activation of T-type channels allowed two retinal input spikes to cause one output spike on average, and we observed almost no instances in which output count exceeded input count (a “burst”). T-type calcium channels therefore help to maintain a single optimal mode of transmission rather than creating a second mode. More fundamentally our results support the general theory, which seeks to predict the properties of a neuron's ion channels and synapses given knowledge of natural patterns of synaptic input.

The Augmentation of Retinogeniculate Communication during Thalamic Burst Mode

“…Burst and tonic response modes are often described as binary states, which is an accurate description for the extreme ends of behavioral arousal: tonic mode during active sensory processing and burst mode during sleep and anesthesia. This hard distinction, however, fails to capture thalamic processing during the transition between the two response modes (Deleuze et al, 2012;Hong et al, 2014). In between the extremes of focused sensory processing and slow-wave sleep, the graded deinactivation of the T-channels of a cell may play a previously underappreciated role in visual processing (Mease et al, 2017).…”

“…When this occurs, depolarizing stimuli can activate T-channels to generate a Ca 2ϩ potential (T-potential), which can then trigger a short train of high frequency, Na ϩ -based action potentials. It is important to note that the magnitude of the T-potential and subsequently the number of spikes it triggers depend on the percentage of T-channels in the deinactivated versus the inactivated state, which, in turn, depends on the depth and duration of the preceding hyperpolarization (Deschênes et al, 1984;Destexhe and Sejnowski, 2002;Hong et al, 2014).…”

Theory of optimal balance predicts and explains the amplitude and decay time of synaptic inhibition

“…The theory should predict the properties of voltage-gated ion channels as it did IPSG. For example, the theory correctly predicted the experimental observation that T-type calcium channels are homoeostatic in counterbalancing opponent IPSG in thalamocortical neurons of LGN50. The more general theory proposes differences between sensory and motor neurons, and it correctly predicted evidence that T-type calcium channels are not homoeostatic but cause bursts of spikes in motor thalamus51.…”

T-type calcium channels cause bursts of spikes in motor but not sensory thalamic neurons during mimicry of natural patterns of synaptic input

“…We previously tested this by examining the function of T-type calcium channel (TtCC) in thalamocortical (TC) neurons of the lateral geniculate nucleus (LGN) while mimicking natural conditions. We found that TtCC amplified EPSPs toward spike threshold so that EPSPs may or may not cause spikes, depending on their amplitude ( Hong et al, 2014 ). This supports our theory, according to which TtCC in sensory neurons should help to maximize the causal link between synaptic excitation and spikes without themselves causing spikes, through a process we have termed “predictive homeostasis” ( Fiorillo et al, 2014 ; Hong et al, 2014 ).…”

“…We found that TtCC amplified EPSPs toward spike threshold so that EPSPs may or may not cause spikes, depending on their amplitude ( Hong et al, 2014 ). This supports our theory, according to which TtCC in sensory neurons should help to maximize the causal link between synaptic excitation and spikes without themselves causing spikes, through a process we have termed “predictive homeostasis” ( Fiorillo et al, 2014 ; Hong et al, 2014 ). In this model of a sensory neuron, TtCC are one of many voltage-gated ion channel (VGC) subtypes predicting and counteracting sensory-related synaptic drive so that each spike signals a positive prediction error, in the spirit of “predictive coding” (e.g., Barlow, 1961 ).…”