Adenosine A₁ and A_2A receptors differently control synaptic plasticity in the mouse dorsal and ventral hippocampus

Abstract

The hippocampus is a brain region involved in processing both memory and emotions, through a preferential involvement of the dorsal hippocampus (DH) and ventral hippocampus (VH), respectively. Adenosine A1 and A2A receptors (A1R and A2AR) control both mood and memory, but it is not known if there is a different adenosine modulation of synaptic plasticity along the hippocampal axis. Using adult, C57BL/6 male mice, we show that both A1R and A2AR were more abundant in DH compared with VH. However, recordings of field excitatory postsynaptic potentials at Schaffer collaterals‐CA1 pyramidal synapses revealed that A1R were equi‐effective to inhibit basal excitatory synaptic transmission in DH and VH, but endogenous A1R activation was more effective to depress the probability of release in VH. In contrast, the selective A2AR antagonist (SCH58261, 50 nM) controlled both long‐term potentiation (induced by a high frequency stimulation protocol) and long‐term depression (induced by a low frequency stimulation protocol) selectively in DH rather than VH, whereas the selective A1R antagonist (DPCPX, 100 nM) revealed a similar tonic inhibition of long‐term depression in DH and VH. These findings show a different control of synaptic plasticity by the adenosine modulation system in the dorsal and ventral poles of the hippocampus, which may underlie a different efficiency of the adenosine system to control mood and memory.

Dorsal-Ventral Differences in Modulation of Synaptic Transmission in the Hippocampus

“…The effects of DPCPX were significantly greater in the dorsal than in the ventral hippocampus for moderate (MANOVA, F = 14.52, p < 0.001), and strong CS (MANOVA, F = 15.22, p < 0.001). DPCPX significantly increased baseline fEPSP slope in both dorsal (30.21 ± 5.13%, n = 23, p < 0.001) and ventral hippocampal slices (23.35 ± 9.32%, n = 15, p < 0.05) similarly (independent t-test, p > 0.5), as also previously observed (Reis et al, 2019). fEPSP slope was adjusted to pre-drug levels before performing heterosynaptic stimulation.…”

Neuromodulation and neuroprotective effects of chlorogenic acids in excitatory synapses of mouse hippocampal slices

“…LTP magnitude was quantified as the percentage change between the average slope of the five fEPSPs taken between 50 and 60 min after LTP induction in relation to the average slope of the fEPSP measured during the 10 min that preceded LTP induction. Long term depression (LTD) was induced as previously described 49 , 67 in ventromedial hippocampal slices with 3 trains of 10 min stimulation at 2 Hz separated by 10-min intervals, with recordings performed at 32ºC. LTD magnitude was calculated as the percentage of change of fEPSP slope 50–60 min after completing LTD induction compared to baseline fEPSP (10 min before beginning LTD induction).…”

Basal G-protein-gated inwardly rectifying potassium (Kir3/GirK) channels activity governs synaptic plasticity that supports dorsal hippocampus-dependent cognitive functions

“…Interestingly, HFS elevates GirK channel surface density by NMDARs activation (Chung et al, 2009) explaining why such long-term inhibitory effects are more noticeable at longer times, when mechanisms needed to initiate the LLTP maintenance take place (Hardt et al, 2014). In addition, synaptic plasticity can be modified by changing the level of pre-and postsynaptic GABAB and A1 receptors desensitization via GirK activity (Wetherington and Lambert, 2002;Reis et al, 2019; . CC-BY-NC-ND 4.0 International license perpetuity.…”

“…In fact, their selective pharmacological activation has also shown to facilitate depotentiation of synaptic strength (Fernandez et al, 2017), very likely through GirK channels in a similar mechanism as reported here. Furthermore, basal GirK conductance has been associated to A1R constitutive activity in the hippocampus (Reis et al, 2019;Hill et al, 2020). A1R activation induces a LTP depotentiation to prepare the hippocampus for subsequent synaptic processing and avoid synaptic overload (Izumi and Zorumski, 2019).…”