Neuromodulation of Spike-Timing-Dependent Plasticity: Past, Present, and Future

Pull-Push Neuromodulation of Cortical Plasticity Enables Rapid Bi-Directional Shifts in Ocular Dominance

“…The prevailing interpretation emerging from these studies is that neuromodulators gate cortical plasticity by enhancing sensory perception, and by promoting patterns of cortical activity suitable for plasticity induction via controlling network excitability. This is consistent with a wealth of studies documenting that neuromodulators improve perception in vivo (see Gelbard-Sagiv et al, 2018;Jacob and Nienborg, 2018;McBurney-Lin et al, 2019;Nadim and Bucher, 2014 for reviews) also affect cellular intrinsic excitability and synaptic inhibition to gate the induction of Hebbian plasticity in vitro (see Brzosko et al, 2019;Palacios-Filardo and Mellor, 2019;Pawlak et al, 2010 for reviews). We propose an additional and different mode of action: direct control of the expression, not the induction, of Hebbian plasticity via the Gq/Gs based pull-push metaplasticity mechanism that we previously demonstrated in vitro, in slices.…”

“…Studies in vitro have demonstrated that neuromodulators can gate the induction of Hebbian plasticity by promoting excitability in cortical circuits (for reviews see Brzosko et al, 2019;Foncelle et al, 2018;Frémaux and Gerstner, 2015;Palacios-Filardo and Mellor, 2019;Pawlak et al, 2010). In addition, neuromodulators can also control the expression of synaptic plasticity, affecting its gain and polarity.…”

Single cell plasticity and population coding stability in auditory thalamus upon associative learning

“…Indeed, we find subsets of neurons in all groups of CS plastic neurons that were not US responsive during FC (see Figure S6). This shows that MGB neurons do not necessarily require converging CS and US input (Ryugo and Weinberger, 1978) to drive functional plasticity upon associative learning, arguing for plasticity mechanisms that go beyond classical Hebbian plasticity, which requires coincidence detection on a millisecond timescale (Markram et al, 1997) and might additionally involve slower, neuromodulatory mechanisms (Brzosko et al, 2019;Izhikevich, 2007;Likhtik and Johansen, 2019) similar to amygdala circuits (Grewe et al, 2017;Johansen et al, 2014) or consolidation during sleep (Hennevin et al, 1993).…”

Impaired spatial learning and suppression of sharp wave ripples by cholinergic activation at the goal location

“…This might suggest that the reverse replay of cell sequence in the reward zone is important for learning. However, additional effects of MS cholinergic activation on intracellular signaling cascades and synaptic plasticity (Brzosko et al, 2019) or synaptic inhibition can not be ruled out at this stage (Hasselmo and Sarter, 2011;Haam and Yakel, 2017).…”