Active Action Potential Propagation But Not Initiation in Thalamic Interneuron Dendrites

Abstract

Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments.

Computer-generated holography enhances voltage dye fluorescence discrimination in adjacent neuronal structures

“…[2][3][4][5][6] In addition to arbitrary lateral patterning capabilities, CGH light targeting confined fluorescence excitation to ∼10 μm in the axial direction for light patterns shaped to cover 10 to 20 μm segments of axons and dendrites [ Fig. 1(c) and 1(d)].…”

“…Voltage-sensitive dyes (VSDs) provide an alternative method to track membrane potential and have been effectively imaged with one-photon epifluorescence microscopy to characterize action potential propagation in small diameter axons and dendrites. [1][2][3][4][5][6] Due to the close spatial mingling of neuronal substructures, improving lateral and axial confinement with confocal microscopy could enable discrimination of signals arising from adjacent or overlapping structures; however, the relatively low fractional sensitivity of voltage sensors (dF∕F ∼5% to 20% per 100 mV in brain slices) necessitates excitation densities and collection efficiencies sufficient to overcome high fractional shot noise. [7][8][9] Loss of photon flux through confocal pinhole and lens arrays stipulates extensive signal averaging 10 or long integration times 11 to increase the S/N.…”

Complex regulation of dendritic transmitter release from thalamic interneurons

“…In essence, a single interneuron could have multiple, independent operating input/output devices. However, recent studies indicate that these dendrites are not merely passive cables, but have the ability to propagate somatic generated potentials back into the dendritic arbor via activation of voltage dependent conductances supporting the hypothesis that certain events could in fact produce widespread activation of F2 terminals throughout the dendritic arbor [19,29,30]. Experimental findings indicate that there may be multiple types of inhibitory output from these interneurons (Figure 2), and these different output types could have significant influence on the spatial and/or temporal influence of inhibition on thalamocortical processing.…”

“…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.…”

“…Suprathreshold activation of interneurons at the somatic level can produce action potentials as well as longer lasting Ca 2+ potentials that can backpropagate into the dendritic arbor [19,30]. While the backpropagating action potential could produce a short, synchronous transient depolarization throughout the dendritic arbor, local synaptic inputs did not initiate spikes within the dendritic arbor [30]. In essence, the backpropagating action potential could serve as a synchronous precise “global” output if this transient potential is sufficient to active F2 terminals, which is currently unclear.…”