Effect of adenosine on short-term synaptic plasticity in mouse piriform cortex in vitro: adenosine acts as a high-pass filter

Abstract

We examined the effect of adenosine and of adenosine A1 receptor blockage on short‐term synaptic plasticity in slices of adult mouse anterior piriform cortex maintained in vitro in an in vivo‐like ACSF. Extracellular recording of postsynaptic responses was performed in layer 1a while repeated electrical stimulation (5‐pulse‐trains, frequency between 3.125 and 100 Hz) was applied to the lateral olfactory tract. Our stimulation protocol was aimed at covering the frequency range of oscillatory activities observed in the olfactory bulb in vivo. In control condition, postsynaptic response amplitude showed a large enhancement for stimulation frequencies in the beta and gamma frequency range. A phenomenological model of short‐term synaptic plasticity fitted to the data suggests that this frequency‐dependent enhancement can be explained by the interplay between a short‐term facilitation mechanism and two short‐term depression mechanisms, with fast and slow recovery time constants. In the presence of adenosine, response amplitude evoked by low‐frequency stimulation decreased in a dose‐dependent manner (IC50 = 70 μmol/L). Yet short‐term plasticity became more dominated by facilitation and less influenced by depression. Both changes compensated for the initial decrease in response amplitude in a way that depended on stimulation frequency: compensation was strongest at high frequency, up to restoring response amplitudes to values similar to those measured in control condition. The model suggested that the main effects of adenosine were to decrease neurotransmitter release probability and to attenuate short‐term depression mechanisms. Overall, these results suggest that adenosine does not merely inhibit neuronal activity but acts in a more subtle, frequency‐dependent manner.

Research progress on adenosine in central nervous system diseases

“…Exogenous adenosine can also be used to increase the adenosine concentration, Yuan et al found that the effect of preconditioning with adenosine on brain ischemic tolerance in rats. Perrier et al think that the main effects of adenosine were to decrease neurotransmitter release probability and to attenuate short‐term depression mechanisms. But this use is relatively rare, and it needs to be further examined.…”

Purinergic Signaling in the Vertebrate Olfactory System

“…Expression of A 1 receptors and ecto 5′-nucleotidases has been found in the piriform cortex, pointing to a role of adenosine in neuromodulation (Goodman and Synder, 1982; Trieu et al, 2015). The main targets of adenosinergic modulation in the piriform cortex are excitatory synaptic inputs in pyramidal cell dendrites (Rezvani et al, 2007; Yang et al, 2007; Trieu et al, 2015; Perrier et al, 2019). The somata of pyramidal cells reside in layer II/III of the piriform cortex, while their apical dendritic arbors extend into the superficial layer I (Figure 5B).…”

“…The low ambient adenosine concentration at layer Ib synapses results from slow ATP-to-adenosine conversion due to low abundance of ecto 5′-nucleotidase and lack of synaptic ensheathment by glial cell processes, which provide one major source of ATP in the cortex (Haberly and Behan, 1983; Nevill and Haberly, 2004; Pankratov and Lalo, 2015; Trieu et al, 2015; Yi et al, 2017). Synapses between lateral olfactory tract fibers and pyramidal cell dendrites in layer Ia are not only depressed by adenosine, but can also be facilitated dependent on the frequency of synaptic activation (Perrier et al, 2019). While adenosine has no effect on the amplitude of fEPSP evoked by a train of stimuli at frequencies between 3 and 25 Hz, it strongly facilitates fEPSP at frequencies between 50 and 100 Hz (Perrier et al, 2019).…”

“…Synapses between lateral olfactory tract fibers and pyramidal cell dendrites in layer Ia are not only depressed by adenosine, but can also be facilitated dependent on the frequency of synaptic activation (Perrier et al, 2019). While adenosine has no effect on the amplitude of fEPSP evoked by a train of stimuli at frequencies between 3 and 25 Hz, it strongly facilitates fEPSP at frequencies between 50 and 100 Hz (Perrier et al, 2019). Since the entire range of stimulation frequencies used in that study reflects frequencies naturally occurring during odor perception depending on, e.g., odor concentrations, adenosine might fine-tune odor perception in an intensity-dependent manner.…”

One Seizure Please, Hold the Sprouts: The Role of Hippocampal Mossy Fiber Sprouting in Epilepsy

“…Under normal circumstances, extracellular adenosine, a byproduct of neuronal ATP-driven vesicle release, establishes an inhibitory tone on synaptic terminals expressing the A1 adenosine receptor and provides negative feedback to active synapses. 10 Interestingly, when the authors delivered an adenosine receptor antagonist to sprouted mossy fiber slices from the brains of epileptic mice, they saw no effect on the evoked postsynaptic current. Thus, they concluded that the sprouted mossy fiber synapse lacks the normal inhibitory tone mediated by adenosine, thereby enabling a higher release probability.…”