title: Paired Stimulation for Spike-Timing-Dependent Plasticity in Primate Sensorimotor Cortex.
abstract: Classicin vitrostudies 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 recentin vivoworks 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 stimulationin vivois a viable method to induce STDP between cortical populations, but that factors beyond activation timing must be considered to produce conditioning effects.SIGNIFICANCE STATEMENTPlasticity of neural connections is important for development, learning, memory, and recovery from injury. Cellular mechanisms underlying spike-timing-dependent plasticity have been studied extensivelyin vitroRecentin vivowork has demonstrated results consistent with the previously defined cellular mechanisms; however, the output measure in these studies was typically an indirect assessment of plasticity at the neural level. Here, we show direct plasticity in recordings of neuronal populations in awake, behaving nonhuman primates induced by paired electrical stimulation. In contrast toin vitrostudies, we found that plastic effects were only produced between specific cortical areas. These findings suggest that similar mechanisms drive plasticityin vitroandin vivo, but that cortical architecture may contribute significantly to site-dependent effects.
authors.affiliation: Department of Physiology and Biophysics, Washington National Primate Research Center.|Center for Sensorimotor Neural Engineering, and.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Seeman
authors.affiliation: Department of Physiology and Biophysics, Washington National Primate Research Center.|Center for Sensorimotor Neural Engineering, and.|Department of Bioengineering, University of Washington, Seattle, Washington 98915.
authors.forename: Brian J
authors.identifier: 0000-0002-7716-456X
authors.initials: BJ
authors.lastname: Mogen
authors.affiliation: Department of Physiology and Biophysics, Washington National Primate Research Center.|Center for Sensorimotor Neural Engineering, and.|Department of Bioengineering, University of Washington, Seattle, Washington 98915.
authors.forename: Eberhard E
authors.identifier: 0000-0002-5767-9531
authors.initials: EE
authors.lastname: Fetz
authors.affiliation: Department of Physiology and Biophysics, Washington National Primate Research Center, perl@uw.edu.|Center for Sensorimotor Neural Engineering, and.
authors.forename: Steve I
authors.identifier: 0000-0002-1149-4152
authors.initials: SI
authors.lastname: Perlmutter
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001703:Biophysics; D001931:Brain Mapping; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D008254:Macaca nemestrina; D008297:Male; D009415:Nerve Net / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D066191:Sensorimotor Cortex / Q000166:cytology* / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors; D014851:Wakefulness
keywords: connectivity; evoked potentials; free behavior