Presynaptic Adenosine Receptor-Mediated Regulation of Diverse Thalamocortical Short-Term Plasticity in the Mouse Whisker Pathway

Abstract

Short-term synaptic plasticity (STP) sets the sensitivity of a synapse to incoming activity and determines the temporal patterns that it best transmits. In "driver" thalamocortical (TC) synaptic populations, STP is dominated by depression during stimulation from rest. However, during ongoing stimulation, lemniscal TC connections onto layer 4 neurons in mouse barrel cortex express variable STP. Each synapse responds to input trains with a distinct pattern of depression or facilitation around its mean steady-state response. As a result, in common with other synaptic populations, lemniscal TC synapses express diverse rather than uniform dynamics, allowing for a rich representation of temporally varying stimuli. Here, we show that this STP diversity is regulated presynaptically. Presynaptic adenosine receptors of the A1R type, but not kainate receptors (KARs), modulate STP behavior. Blocking the receptors does not eliminate diversity, indicating that diversity is related to heterogeneous expression of multiple mechanisms in the pathway from presynaptic calcium influx to neurotransmitter release.

Keywords: in vitro; patch clamp; short-term plasticity; somatosensory; tactile; vibrissae; whole-cell.

Figure 1

Short-term synaptic plasticity (STP) diversity depends on presynaptic mechanisms. (A) Example of recording of post-synaptic potential (PSP) responses to ongoing thalamocortical (TC) stimulation (mean of eight traces). Scale bars: 300 ms, 0.5 mV. Dots at bottom, times of stimulation. Stimulation at constant frequency shown in yellow; stimulation just after transition to irregular train, in magenta; later irregular stimulation, in gray. The facilitation index was obtained by dividing the average response just after switching to irregular stimulation (magenta dots) by the average steady-state response at constant frequency (yellow dots). (B) Facilitation index dependance on extracellular [Ca²⁺]. In (B–E), each connected pair of points is one recording. Bars represent population median. Asterisks denote statistically significant difference between distributions (tests are indicated in main text). Facilitation index values decrease and become more narrowly distributed as [Ca²⁺] increases. (C) Tuning curve slope (TCS) dependance on extracellular [Ca²⁺]. Distribution becomes narrower as [Ca²⁺] increases. (D) Kynurenic acid partial block of postsynaptic glutamate receptors decreases EPSP size. (E) Kynurenic acid application has no systematic effect on facilitation index. (F) Kynurenic acid has no systematic effect on TCS.

Figure 2

STP distribution is regulated by A1 adenosine receptor activation. Each connected pair of points is one recording. Bars represent population median. Asterisks denote statistically significant difference between distributions (tests are indicated in main text). (A) Adenosine application increases paired pulse ratio. (B) Adenosine application increases facilitation index. (C) Adenosine has no systematic effect on TCS. (D) A1 receptor blockade by DPCPX (top) or CPT (bottom) has no systematic effect on facilitation index. (E) A1 receptor blockade by DPCPX (top) or CPT (bottom) increases TCS.

Figure 3

STP distribution is not consistently affected by kainate receptor activation. Each connected pair of points is one recording. Bars represent population median. (A) No significant effect on facilitation index (left) or on TCS (right) of application of UBP 310, a specific blocker of GluK1-containing receptors. (B) No significant effect on facilitation index (left) or on TCS (right) of application of NS-102, a specific blocker of GluK2-containing receptors.