Adenosine Differentially Modulates Synaptic Transmission of Excitatory and Inhibitory Microcircuits in Layer 4 of Rat Barrel Cortex

Abstract

Adenosine is considered to be a key regulator of sleep homeostasis by promoting slow-wave sleep through inhibition of the brain's arousal centers. However, little is known about the effect of adenosine on neuronal network activity at the cellular level in the neocortex. Here, we show that adenosine differentially modulates synaptic transmission between different types of neurons in cortical layer 4 (L4) through activation of pre- and/or postsynaptically located adenosine A1 receptors. In recurrent excitatory connections between L4 spiny neurons, adenosine suppresses synaptic transmission through activation of both pre- and postsynaptic A1 receptors. In reciprocal excitatory and inhibitory connections between L4 spiny neurons and interneurons, adenosine strongly suppresses excitatory transmission via activating presynaptic A1 receptors but only slightly suppresses inhibitory transmission via activating postsynaptic A1 receptors. Adenosine has no effect on inhibitory transmission between L4 interneurons. The effect of adenosine is concentration dependent and first visible at a concentration of 1 μM. The effect of adenosine is blocked by the specific A1 receptor antagonist, 8-cyclopentyltheophylline or the nonspecific adenosine receptor antagonist, caffeine. By differentially affecting excitatory and inhibitory synaptic transmission, adenosine changes the excitation-inhibition balance and causes an overall shift to lower excitability in L4 primary somatosensory (barrel) cortical microcircuits.

Unveiling the Synaptic Function and Structure Using Paired Recordings From Synaptically Coupled Neurons

“…The adenosine effect is most likely mediated by A 1 adenosine receptors located in presynaptic axonal terminals; they induce a reduction in the open probability of presynaptic Ca 2+ channels involved in triggering the release of neurotransmitters. This effect is already apparent at low endogenous concentrations of adenosine (∼1 µM) which are tonically released (Qi et al, 2017). In contrast, adenosine has a much smaller effect on inhibitory synaptic transmission onto excitatory neurons: here, only the IPSP time course is altered due to activation of postsynaptically located A 1 adenosine receptors.…”

“…Overlay of average EPSPs recorded under three recording conditions: control (black), 100 µM adenosine (purple), and 100 µM adenosine plus 5 µM 8-cyclopentyltheophylline (CPT), a specific adenosine A1 receptor antagonist (gray) are shown for four connection types. (A-D) have been adapted from Eggermann and Feldmeyer (2009) with permission and (E) from Qi et al (2017) with permission.…”

“…Adenosine has been suggested to play an important role in the sleep homeostasis (Porkka-Heiskanen et al, 1997. Recently, the effect of adenosine on synaptic transmission has been assessed using paired recordings (Kerr et al, 2013;Qi et al, 2017). Adenosine induces a suppression of the neurotransmitter release probability at intralaminar L2/3, L4, and L5 and translaminar L4-L2/3 excitatory connections.…”

Visual imagery and visual perception induce similar changes in occipital slow waves of sleep

“…However, changes in SWA may also reflect changes in on the neuromodulatory tone and the balance between excitation and inhibition, independent of changes in synaptic strength (Cirelli, 2017;Frank & Cantera, 2014). Moreover, the wake-dependent accumulation of metabolites and of molecular factors reflecting an increased cellular stress have been also suggested to potentially affect SWA at both global and local level (Krueger et al, 2008;Qi et al, 2016;Vyazovskiy & Harris, 2013;Wang et al, 2018).…”

Efeitos da ingestão de cafeína sobre o desempenho de ciclistas mentalmente fadigados durante um teste de ciclismo contrarrelógio de 20km

“…Tem sido proposto que o CPF desempenhe um papel importante na regulação do ritmo do exercício, já que o CPF está envolvido em um comportamento pró-ativo direcionado por objetivos (EKKEKAKIS, 2009;COHEN, 2001;PIRES et al, 2016). MARTIN et al, 2018;QI et al, 2017). Assim, também hipotetizamos que a ingestão de CAF poderia atenuar os efeitos de fadiga mental, uma vez que a CAF bloqueia os receptores neuronais de adenosina A1 e melhora a atividade neuronal e a excitabilidade do SNC (DAVIS et al, 2003;CAFARELLI, 2004 (LIU, 2017;WAGER et al, 2004).…”