Quantal events shape cerebellar interneuron firing

Abstract

Many small synaptic inputs or one large input are needed to influence principal cell firing, whereas individual quanta exert little influence. However, the role of a quantum may be greater for small interneurons with high input resistances. Using dynamic clamp recordings, we found that individual quanta strongly influence rat cerebellar stellate cell firing. When the frequency of synaptic inputs was low, the timing of recent spikes regulated the influence of excitatory quanta. In contrast, when input frequency was high, spike timing was less important than interactions with other inputs. Inhibitory quanta rapidly terminated firing, whereas small numbers of coincident excitatory quanta reliably and rapidly triggered firing. Our results suggest that stellate cells achieve temporal precision through coincidence detection and disynaptic inhibition, despite their high resistances and long membrane time constants. Thus, we propose that small interneurons can process synaptic inputs in a fundamentally different way from principal cells.

Impact of single-site axonal GABAergic synaptic events on cerebellar interneuron activity

“…Our immunolabeling results show that a significant number of varicosities are localized close to the soma and may therefore influence the membrane potential (Vm) in the axon initial segment (AIS) substantially. This, together with the fact that MLIs have a high input resistance (Midtgaard, 1992;Llano and Gerschenfeld, 1993), made us hypothesize that single axonal synaptic events, although filtered, may strongly influence neuronal firing (as was shown previously for somatodendritic glutamatergic events; Carter and Regehr, 2002). A first indication that this is indeed the case appeared when performing the experiments in Fig.…”

“…Together with subthreshold somatodendritic depolarizations, ASPs lead to a drastic increase in P spike that very often leads to AP firing. These results are not surprising considering that MLIs are small, electrically compact cells with high input resistances (>1 GΩ; Llano and Gerschenfeld, 1993), where single synaptic inputs can shape cell firing (Carter and Regehr, 2002).…”

“…Although the role of the AP-dependent activation of axonal autoRs has already been addressed , the impact of spontaneous miniature axonal synaptic events remains unknown. Understanding the physiological role and the mechanisms of action of these miniature events is extremely important: in electrically compact cells like MLIs, individual somatodendritic quantal events strongly affect spiking behavior (Carter and Regehr, 2002), suggesting that axonal preminis could also make an important contribution to the cell's activity.…”

Neurotrophin signaling among neurons and glia during formation of tripartite synapses

“…At hippocampal and cortical synapses in vivo and in vitro, BDNF facilitates long-term potentiation, attenuates long-term depression and promotes homeostatic and competitive interactions that refine neural circuitry (Korte et al, 1995;Akaneya et al, 1996;Cabelli et al, 1996;Huang et al, 1999;Turrigiano and Nelson, 2000;Turrigiano and Nelson, 2004). At hippocampal and cerebellar synapses in BDNF-deficient mice, high-frequency stimulation and paired-pulse facilitation are impaired, which is consistent with compromised presynaptic release (Pozzo-Miller et al, 1999;Carter and Regehr, 2002). These studies demonstrate that BDNF acts presynaptically to modulate the dynamics of glutamate release at developing and mature synapses.…”

Mind-altering miniature neurotransmitter release?

“…Typically miniature release only occurs at a frequency of a few hertz within a neuron and is of insufficient amplitude to evoke a postsynaptic action potential in a principal neuron by itself. However, the firing of electrically compact interneurons (that are close to threshold) can be influenced by individual quantal release events (25). These findings raise the question of what the functional significance of miniature synaptic activity is in large principal neurons.…”