Does Insufficient Development Excitatory Activity Fail to Recruit Inhibitory Activity?
Abstract
The objective of this proposal is to explore the nature and extent of a developmental role for inhibitory neuron roles in establishing functional neural networks in vitro, and the consequences of failure to establish the normal balance of excititatory and inhibitory activity on network activity. The proposal lays out a plan to monitor network activity of maturing cultured embryonic cortical neurons with an existing microelectrode array system embedded into the culture dish. Simultaneously, calcium influx into identified excitatory and inhibitory neurons will be monitored optically via phase-contrast epifluorescence. Electrode location and number will be varied to incorporate different inputs into the cultured network and will be coupled with the administration of GABAergic and glutamergic channel antagonists and the neurotransmitters themselves as additional variables. We stimulated developing networks with a recorded synaptic signal via a "complete" regiment (5 continuous days of stimulation, based on our prior studies) or an "incomplete" regimen (a single day of stimulation). Spontaneous signaling was recorded prior to and following the above stimulations, along with recording of unstimulated (control) networks. Our findings demonstrated that complete stimulation hastened maturation of networks as defined by establishing the normal balance of excitatory and inhibitory neurons. By contrast, incomplete stimulation fostered persistence of epileptiform signaling characteristic of immature cultures. These studies support the requirement for inhibitory neurons in establishment of mature signaling (and therefore maturation of the network). They further leave open the possibility that developmental insufficiency in excitatory signaling may foster persistent nervous system disorders such as epilepsy.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 12, 2017
- Source ID
- W911NF1510206
Entities
People
- Thomas Shea
Organizations
- Army Contracting Command
- United States Army
- University of Massachusetts