Figure 3. Overarching hypothesis of critical period regulation.

The circuit mechanism of cortical disinhibition and the synaptic mechanism of thalamocortical (TC) LTP/LTD regulation by adenosine may work cooperatively to mediate neuromodulatory inputs to the auditory cortex to manage cortical map plasticity and timing of the critical period. We hypothesize that refinement of tonotopic inputs from the auditory thalamus [ventral part of the medial geniculate body (MGBv)] is regulated at TC projections by adenosine signaling, whereas cortical disinhibition acts as a nonselective gate. Several questions remain about how (if at all) these combined mechanisms interact and whether other neuromodulators, such as dopamine from the ventral tegmental area (VTA) and norepinephrine from the locus coeruleus (LC) are involved.