Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

Abstract

Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. Here we show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5′-nucleotidase–dependent adenosine production or A1 adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement of tone-discrimination abilities. We conclude that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.

Adenosine A1 Receptor mRNA Expression by Neurons and Glia in the Auditory Forebrain

“…These results indicate that A 1 R-adenosine signaling could impact the presynaptic activity of TC projections MG to all areas of auditory cortex (primary and secondary), as well as descending projections to auditory brainstem (e.g., inferior colliculus). These patterns are consistent with autoradiographic binding studies of A 1 Rs in several species (Fastbom et al, 1987), and also support recent observations (discussed above) that A 1 Rs located on TC terminals in L3/L4 of A1 modulate presynaptic glutamate release with profound effects on excitatory transmission and synaptic plasticity Chun et al, 2013;Blundon et al, 2017).…”

“…Moreover, these effects can vary regionally by neuronal subpopulation and A 1 R expression density (Lee et al, ; Kim and Johnston, ), indicating that properties may vary by specific location or cell type. As mentioned above, induction of LTD, LTP and receptive field plasticity in auditory cortex was distinct for pre‐ and postsynaptic A 1 Rs (Blundon et al, ; Chun et al, ; Blundon et al, ), highlighting potential differences in pre‐ or postsynaptic A 1 R‐adenosine signaling.…”

“…In A 1 R −/− knockout mice, LTP could be induced even when M 1 Rs were blocked, indicating that the cholinergic inputs are not required when A 1 Rs have been removed. Most recently, this line of work was extended by this group to receptive field plasticity, in vivo (Blundon et al, ). As noted above, passive exposure to a pure tone in an enriched acoustic environment is sufficient to alter receptive fields and expand map representation of that tone in A1 neurons of immature animals, but not adults.…”

“…It may be significant that while plasticity becomes gated at mature TC synapses, cortico‐cortical synapses remain plastic after critical periods close (Amitai, ; Froemke et al, ; Jiang et al, ; Oswald and Reyes, , ; Huang et al, ), suggesting different regulatory mechanisms for TC and CC projections. Indeed, whereas interference with A 1 R‐adenosine signaling in MG was sufficient to restore cortical map plasticity, the same manipulations at corticocortical synapses in A1 were not (Blundon et al, ). The reasons remain unknown.…”

“…Consistent with the foregoing, recent studies of thalamocortical (TC) inputs to sensory cortex have revealed that adenosine functions as a negative regulator of glutamate release via activation of presynaptic A 1 receptors (Fontanez and Porter, ; Bayazitov et al, ; Blundon et al, ; Chun et al, ; Ferrati et al, ). In the auditory forebrain, restriction of A 1 ‐mediated adenosine signaling in medial geniculate (MG) neurons is sufficient to extend LTP, LTD, and tonotopic map plasticity in adult mice for months beyond the critical period (Blundon et al, ; Chun et al, ; Blundon et al, ). In contrast, restricting adenosine signaling in neurons of the primary auditory cortex (A1) does not contribute to these forms of plasticity, suggesting that the effects are confined to presynaptic TC projections.…”