Paired Stimulation for Spike-Timing-Dependent Plasticity in Primate Sensorimotor Cortex

Abstract

Classic in vitro studies have described spike-timing-dependent plasticity (STDP) at a synapse: the connection from neuron A to neuron B is strengthened (or weakened) when A fires before (or after) B within an optimal time window. Accordingly, more recent in vivo works have demonstrated behavioral effects consistent with an STDP mechanism; however, many relied on single-unit recordings. The ability to modify cortical connections becomes useful in the context of injury, when connectivity and associated behavior are compromised. To avoid the need for long-term, stable isolation of single units, one could control timed activation of two cortical sites with paired electrical stimulation. We tested the hypothesis that STDP could be induced via prolonged paired stimulation as quantified by cortical evoked potentials (EPs) in the sensorimotor cortex of awake, behaving monkeys. Paired simulation between two interconnected sites produced robust effects in EPs consistent with STDP, but only at 2/15 tested pairs. The stimulation protocol often produced increases in global network excitability or depression of the conditioned pair. Together, these results suggest that paired stimulation in vivo is a viable method to induce STDP between cortical populations, but that factors beyond activation timing must be considered to produce conditioning effects.

Targeted cortical reorganization using optogenetics in non-human primates

“…Recently these results were reproduced in a modeling work at the network level ( Lajoie et al, 2017 ). Similar results have been observed using open-loop stimulation protocols to induce targeted plasticity between two cortical sites ( Rebesco and Miller, 2011 ; Seeman et al, 2017 ). Notably, these papers have reported off-target effects, but these were either interpreted as global changes in excitability or were not explained.…”

“…To evaluate stimulation-induced changes across these areas we investigated two measures of functional connectivity, one based on stimulation and one based on natural neural processing. Variants of SERR ( Seeman et al, 2017 ; Feldmeyer and Sakmann, 2000 ; Klinshov et al, 2014 ) and coherence ( Bastos and Schoffelen, 2015 ; Lang et al, 2012 ) have been used previously to evaluate functional connectivity. However, to our knowledge they have never been used in combination or compared.…”

“…Previous work has demonstrated that either activity dependent ( Jackson et al, 2006 ; Lucas and Fetz, 2013 ; Nishimura et al, 2013 ; Rebesco et al, 2010 ; Song et al, 2013 ) or paired electrical stimulation ( Rebesco and Miller, 2011 ; Seeman et al, 2017 ) can lead to plastic changes in both primate and rodent cortex. Here we demonstrated that optogenetic stimulation at even a single location strengthens inter-area functional connectivity between brain areas.…”

“…Despite the extensive work studying Hebbian plasticity at the cellular level, it remains unclear how synaptic plasticity leads to large-scale functional reorganization. Recently, several studies have shown large-scale plasticity following brain stimulation that is consistent with Hebbian mechanisms ( Jackson et al, 2006 ; Lucas and Fetz, 2013 ; Seeman et al, 2017 ; Nishimura et al, 2013 ; Rebesco and Miller, 2011 ; Rebesco et al, 2010 ; Song et al, 2013 ; Lajoie et al, 2017 ). In particular, Fetz and colleagues implemented an activity-dependent stimulation protocol, effectively introducing an artificial connection between two sites in the motor cortex ( Jackson et al, 2006 ; Lucas and Fetz, 2013 ).…”

Induction of plasticity in the human motor system by motor imagery and transcranial magnetic stimulation

“…This monosynaptic response would occur at short and fixed latency, possibly leading to the generation of STDP without precisely paired stimuli. Even using invasive cortical microstimulation through implanted electrodes, Seeman et al (2017) found that only a minority of tested sites exhibited plasticity dependent on timing as expected by STDP. It is known that delivering cortical stimulation to coincide with overt movement can lead to plastic changes (Thabit et al 2010;Lucas & Fetz, 2013;Edwardson et al 2014;Buetefisch et al 2015).…”