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We propose that to fully understand biological mechanisms underlying pathological brain activity with transitions (e.g., into and out of seizures), wide-bandwidth electrophysiological recordings are important. We demonstrate the importance of ultraslow potential shifts and infraslow oscillations for reliable tracking of synaptic physiology, within a neural mass model, from brain recordings that undergo pathological phase transitions. We use wide-bandwidth data (direct current (DC) to high-frequency activity), recorded using epidural and penetrating graphene micro-transistor arrays in a rodent model of acute seizures. Using this technological approach, we capture the dynamics of infraslow changes that contribute to seizure initiation (active pre-seizure DC shifts) and progression (passive DC shifts). By employing a continuous-discrete unscented Kalman filter, we track biological mechanisms from full-bandwidth data with and without active pre-seizure DC shifts during paroxysmal transitions. We then apply the same methodological approach for tracking the same parameters after application of high-pass-filtering >0.3Hz to both data sets. This approach reveals that ultraslow potential shifts play a fundamental role in the transition to seizure, and the use of high- pass-filtered data results in the loss of key information in regard to seizure onset and termination dynamics. [ABSTRACT FROM AUTHOR]

We propose that to fully understand biological mechanisms underlying pathological brain activity with transitions (e.g., into and out of seizures), wide-bandwidth electrophysiological recordings are important. We demonstrate the importance of ultraslow potential shifts and infraslow oscillations for reliable tracking of synaptic physiology, within a neural mass model, from brain recordings that undergo pathological phase transitions. We use wide-bandwidth data (direct current (DC) to high-frequency activity), recorded using epidural and penetrating graphene micro-transistor arrays in a rodent model of acute seizures. Using this technological approach, we capture the dynamics of infraslow changes that contribute to seizure initiation (active pre-seizure DC shifts) and progression (passive DC shifts). By employing a continuous–discrete unscented Kalman filter, we track biological mechanisms from full-bandwidth data with and without active pre-seizure DC shifts during paroxysmal transitions. We then apply the same methodological approach for tracking the same parameters after application of high-pass-filtering >0.3Hz to both data sets. This approach reveals that ultraslow potential shifts play a fundamental role in the transition to seizure, and the use of high-pass-filtered data results in the loss of key information in regard to seizure onset and termination dynamics.

The sparse connectivity within the striatum in vivo makes the investigation of individual corticostriatal synapses very difficult. Most studies of the corticostriatal input have been done using electrical stimulation under conditions under which it is hard to identify the precise origin of the cortical input. We have employed an in vitro dissociated cell culture system that allows the identification of individual corticostriatal pairs and have been developing methods to study individual cortical neuron inputs to striatal neurons.In mixed corticostriatal cultures, neurons had resting activity similar to the system in vivo. Up/down states were obvious and seemed to encompass the entire culture. Mixed cultures of cortical neurons from transgenic mice expressing green fluorescent protein (GFP) with striatal neurons from wild-type mice of the same developmental stage allowed visual identification of individual candidate corticostriatal pairs. Recordings were performed between 12 and 37 days in vitro (DIV).To investigate synaptic connections we recorded from 69 corticostriatal pairs of which 44 were connected in one direction and 25 reciprocally. Of these connections 41 were corticostriatal (9 inhibitory) and 53 striatocortical (all inhibitory). The observed excitatory responses were of variable amplitude (-10 to -370 pA, n=32). We found the connections very secure – with negligible failures on repeated (approx. 1Hz) stimulation of the cortical neuron. Inhibitory corticostriatal responses were also observed (-13 to -314pA, n=9). Possibly due to the mixed type of culture we found an inhibitory striatocortical response (-14 to -598pA, n=53). We are now recording from neurons in separate compartments to more closely emulate neuroanatomical conditions but still with the possibility of the easier identification of the connectivity.