Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

Abstract

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

Optogenetically induced sleep spindle rhythms alter sleep architectures in mice

“…Moreover, in vitro recordings from TRN neurons showed that spindle-like photostimuli could reliably evoke repetitive burst firing activity, which is comparable to the rhythmic spike-burst activity of TRN neurons (5,23,24). This is an intrinsic firing pattern of TRN neurons during NREM sleep and is hypothesized to be the main factor that drives generation of sleep spindles (4,23).…”

“…Such stimuli were repeated at intervals of 7.5 s, the average interval between sleep spindles (2,4). A second stimulus protocol consisted of 200-ms-duration light flashes repeated at 1 Hz (i.e., 1-Hz protocol); these were intended to mimic slow wave responses during NREM sleep (23)(24)(25). Finally, we used a third photostimulation protocol consisting of 20-ms-duration stimuli repeated at 0.1 Hz that has been previously reported to produce thalamic bursts and cortical spindles in vivo (i.e., pulse protocol) (18).…”

Action potential threshold of wide dynamic range neurons in rat spinal dorsal horn evoked by manual acupuncture at ST36

“…6 gives the distribution of spike thresholds for the neurons of one rat in the case of three acupuncture frequencies. To measure threshold variation, we compute the standard deviation of each voltage threshold distribution [31,33]. It is found that the variability in spike threshold evoked by 30 times/min acupuncture (12:1179 mV, n¼ 220) is not different to the ones evoked by acupuncture with 60 times/min (11:9873 mV, n¼323) or 120 Fig.…”

“…If it is below the threshold, the neuron remains quiescent. In many neurons, the spike threshold is not constant but dynamic, which varies with neuronal recent spiking behaviors, such as the preceding rate of depolarization, the average membrane potential, or the preceding interspike interval [27][28][29][30][31][32][33][34][35][36]. The dynamic spike threshold could be regulated by ionic channel kinetics, such as Na þ channel inactivation and K þ channel activation [27][28][29]31,32,35].…”

“…The dynamic spike threshold could be regulated by ionic channel kinetics, such as Na þ channel inactivation and K þ channel activation [27][28][29]31,32,35]. It plays a crucial role in action potential initiation, and it is also critically important in the process of encoding stimulus signals by a neuron [27][28][29][30][31][32][33]35]. Then, investigating the threshold properties of the action potentials evoked by acupuncture at ST36 could facilitate the interpretation of how acupuncture signals are encoded in its neural pathway, which may help to address the above-mentioned important questions.…”