Exploring the Impact of Activity-Dependent Stimulation on Neuroanatomy

Abstract

Background: Activity-dependent stimulation (ADS) uses recorded neural activity to trigger stimulation of the brain. Open-loop stimulation (OLS) is independent of neural feedback, thus relying on a machine-generated pattern of stimulation. A previous study found that ADS and OLS both promote fine motor control recovery in a rat model of traumatic brain injury in the primary motor cortex. ADS enhanced recovery of motor function compared to OLS. Investigation of the underlying mechanisms driving motor recovery in response to ADS and OLS is needed. Methods: Six healthy, adult male rats were implanted with recording electrodes in the premotor cortex (PM) and stimulating electrodes in the somatosensory cortex (S1). Three of the rats were treated with ADS; action potentials (spikes) recorded in the premotor cortex triggered stimulation in S1. Three rats were treated with random OLS mimicking the same rate of stimulation as ADS. After 21 days of stimulation, brain tissue was processed for evidence of morphological differences between the two types of stimulation. Immunohistochemistry was used to label sections for synaptophysin, BDNF, GluR1, and GluR2. Densitometry was used for semiquantitative analysis. Results: As this was a pilot study with a small sample size, analyses were exploratory. Observed synaptophysin and GluR1 immunoreactivity (IR) was greater in ADS rats compared to OLS rats (p=0.0253 and p=0.0253 respectively), whereas BDNF and GluR2 lacked such trends (p=0.456 and p=0.456 respectively). In all rats the stimulated hemispheres expressed significantly more synaptophysin (p= 0.0132) and GluR1 (p=0.0062) than the non-stimulated hemispheres. BDNF and GluR2 expression were significantly lower in the stimulated hemispheres (p=0.0030 and p=0.0054 respectively). Conclusions: The data suggests that ADS and OLS both enhance synaptogenesis and GluR1 expression. Results are consistent with the hypothesis that ADS induces greater synaptogenesis and GluR1 expression than OLS. Data does not support the hypothesis that BDNF expression is higher after ADS treatment than OLS treatment. This pilot study elucidates the impact of intracortical stimulation on synaptic plasticity in the cerebral cortex.