Active Dendritic Conductances Dynamically Regulate GABA Release from Thalamic Interneurons

Abstract

Inhibitory interneurons in the dorsal lateral geniculate nucleus (dLGN) process visual information by precisely controlling spike timing and by refining the receptive fields of thalamocortical (TC) neurons. Previous studies indicate that dLGN interneurons inhibit TC neurons by releasing GABA from both axons and dendrites. However, the mechanisms controlling GABA release are poorly understood. Here, using simultaneous whole-cell recordings from interneurons and TC neurons and two-photon calcium imaging, we find that synchronous activation of multiple retinal ganglion cells (RGCs) triggers sodium spikes that propagate throughout interneuron axons and dendrites, and calcium spikes that invade dendrites but not axons. These distinct modes of interneuron firing can trigger both a rapid and a sustained component of inhibition onto TC neurons. Our studies suggest that active conductances make LGN interneurons flexible circuit-elements that can shift their spatial and temporal properties of GABA release in response to coincident activation of functionally related subsets of RGCs.

The sleep relay—the role of the thalamus in central and decentral sleep regulation

“…The ascending fibres from the brainstem and the corticofugal axons are capable of controlling the strength and pattern of intrathalamic inhibitory mechanisms [106,176,177]. GABA release in these interneurons occurs in both axons and dendrites and while Na + APs evoke widespread Ca 2+ signals throughout dendritic and axonal arbours, Ca 2+ spikes mediated by L-type Ca 2+ channels specifically trigger dendritic GABA release [1]. These Na + and Ca 2+ spikes regulate the rapid and prolonged release of GABA from interneurons, determining spatial and temporal features of the feedforward inhibition [11].…”

Comparison of baroreceptive to other afferent synaptic transmission to the medial solitary tract nucleus

“…Once the axon threshold is exceeded, conducted action potentials are intensity independent. The all-or-none character of ST intensity-recruitment relations indicates a reliance on activation of single axons impinging on individual neurons (1,8). For testing, shock intensities were finely graded above and below threshold to establish the threshold value for the onset of reliably evoked responses.…”

Complex regulation of dendritic transmitter release from thalamic interneurons

“…Whether these specific subtypes can be selectively activated by synaptic afferents remains unclear, but could have important consequences on our understanding of mGluR-dependent actions on thalamocortical processing. This is an relatively important issue consider that over the last several years, the independence between the distal events and somatic activity of the dLGN interneurons has been questioned based on studies indicating that somatic events can backpropagate into the dendritic arbor of the interneurons [19,29,30]. The functional significance of these differences is further discussed below ( Local vs.…”

“…Several different approaches including electrical stimulation of synaptic inputs, local pressure application of pharmacological agonists, and photo-uncaging of caged glutamate have demonstrated that iGluR activation produces a short-lasting robust increase in potential F2 output. The iGluR-dependent response has a short latency and relatively short duration (typically <100ms) [19]. In contrast, the mGluR-dependent response has a longer latency and can have a duration of tens of seconds [21].…”

“…Recently, it has been shown that optic tract stimulation can evoke an EPSP with a lasting depolarizing plateau (~100 ms duration) that is dependent on activation of L-type calcium channels in mouse dLGN interneurons [19]. In a subsequent study, strong tetanic stimulation could produce long-lasting action potential discharge in these interneurons, which could be associated with a prolonged depolarizing plateau potential (>10 s duration) and associated increase in inhibitory output [29].…”