Modulation of Transmission during Trains at a Cerebellar Synapse

Abstract

Activity-dependent processes dynamically regulate synapses on the time scale of milliseconds to seconds. Here, we examine the factors governing synaptic strength during repetitive stimulation, both in control conditions and during presynaptic inhibition. Field recordings of presynaptic volleys, optical measurements of presynaptic calcium, and voltage-clamp recordings of postsynaptic currents were used to examine parallel fiber to Purkinje cell synapses in cerebellar brain slices at 34°C. In control conditions, regular stimulus trains (1-50 Hz) evoked up to a 250% peak synaptic enhancement, whereas during irregular stimulation, a threefold variability in EPSC amplitude was observed. When initial EPSC amplitudes were reduced by 50%, either by lowering external calcium or by activating adenosine A 1 or GABA B receptors, the peak enhancement during regular trains was 500%, and synaptic variability during irregular trains was nearly sixfold. By contrast, changes in fiber excitability and calcium influx per pulse were small during trains. Presynaptic calcium measurements indicated that by pulse 10, stimulusevoked calcium influx had increased by ϳ15%, which on the basis of the measured relationship between calcium influx and release corresponds to an EPSC enhancement of 50%. This enhancement was the same in all experimental conditions, even in the presence of N 6 -cyclopentyladenosine or baclofen, suggesting that repetitive stimulation does not relieve the G-protein inhibition of calcium channels by these modulators. Therefore, for our experimental conditions, changes in synaptic strength during trains are primarily attributable to residual calcium (Ca res )-dependent short-term plasticities, and the actions of neuromodulators during repetitive stimulation result from their inhibition of initial calcium influx and the resulting effects on Ca res and calcium-driven processes.

GABA B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

“…GABA B Rs enable inactivity-induced homeostatic increase in synaptic strength by three principle mechanisms: promoting synatxin-1 conformational switch to enhance SNAREcomplex assembly, augmenting presynaptic Ca 2+ flux to promote spike-evoked vesicle exocytosis, and increasing the quantal excitatory amplitude. Thus, GABA B Rs, in addition to modulation of short-term (32,33) and long-term, Hebbian (21) synaptic plasticity, are essential for maintaining firing stability of neural circuits.…”

Dopamine Modulates Use-Dependent Plasticity of Inhibitory Synapses

“…Furthermore, in the supraoptic nucleus (SON), dopamine directly depolarizes MNCs (Yang et al, 1991) and decreases the release of both GABA (Azdad et al, 2003) and the excitatory neurotransmitter glutamate (Price and Pittman, 2001). In other brain regions, neurotransmitter release is also regulated dynamically by the rate at which the nerve terminal is activated (Tsodyks and Markram, 1997;Thomson and Bannister, 1999;Dittman et al, 2000;Kreitzer and Regehr, 2000;Hefft et al, 2002;Telgkamp and Raman, 2002). We hypothesized that a similar, short-term synaptic plasticity may be an important determinant of information transfer at hypothalamic synapses.…”

“…We hypothesized that a similar, short-term synaptic plasticity may be an important determinant of information transfer at hypothalamic synapses. Furthermore, because this plasticity is sensitive to changes in the release probability (P r ) (Tsodyks and Markram, 1997;Kreitzer and Regehr, 2000), we reasoned that a compound, such as dopamine, should affect the development of this plasticity. To test this hypothesis, we obtained whole-cell recordings from MNCs in the PVN.…”

Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step

“…Repetitive activation of afferent fibers and synapses can induce eCB retrograde signaling through stimulation of mechanisms needed for postsynaptic eCB synthesis (3,12,(27)(28)(29)(30)(31) and by providing a synergistic presynaptic signal necessary for LTD induction (2,28,(32)(33)(34). However, it is not clear whether afferent/synaptic activation plays any role in the eCB release process.…”