Temporal Coordination of Hippocampal Neurons Reflects Cognitive Outcome Post-febrile Status Epilepticus

Abstract

The coordination of dynamic neural activity within and between neural networks is believed to underlie normal cognitive processes. Conversely, cognitive deficits that occur following neurological insults may result from network discoordination. We hypothesized that cognitive outcome following febrile status epilepticus (FSE) depends on network efficacy within and between fields CA1 and CA3 to dynamically organize cell activity by theta phase. Control and FSE rats were trained to forage or perform an active avoidance spatial task. FSE rats were sorted by those that were able to reach task criterion (FSE-L) and those that could not (FSE-NL). FSE-NL CA1 place cells did not exhibit phase preference in either context and exhibited poor cross-theta interaction between CA1 and CA3. FSE-L and control CA1 place cells exhibited phase preference at peak theta that shifted during active avoidance to the same static phase preference observed in CA3. Temporal coordination of neuronal activity by theta phase may therefore explain variability in cognitive outcome following neurological insults in early development.

Why Are Children With Epileptic Encephalopathies Encephalopathic?

“…These key features of memory are coordinated by theta phase, which temporally organizes the transfer of neural information between the hippocampus and neocortex and within the hippocampal circuit 83;84 . In accordance with this body of work, we have recently shown the translational relevance of the “temporal coordination hypothesis”, which simply states that the dynamic temporal coordination of neurons within and between relevant circuits underpins learning and memory 40 . We have shown that levels of temporal coordination among neurons in the hippocampal circuit by theta oscillations depend on levels of cognitive demand, and reflect cognitive outcome post febrile status epilepticus.…”

“…FSE-L and control CA1 place cells exhibited phase preference at peak theta that shifted during active avoidance to the same static phase preference observed in CA3. These results therefore imply that the dynamic organization of CA1 neurons within theta enable communication within the hippocampal circuit that is necessary for the performance of a complex spatial task 40 .…”

Efficacy of nonselective optogenetic control of the medial septum over hippocampal oscillations: the influence of speed and implications for cognitive enhancement

“…The temporal discoordination of CA1 place cell action potentials with respect to local theta oscillations was also found to correlate with learning deficits on a complex spatial task (Barry et al. ).…”

“…; Siegle and Wilson ; Barry et al. ). Specifically, both modeling and experimental work suggest that the dynamic phase relationships of synaptic current as well as the timing of action potentials during theta rhythm are critical in both encoding and retrieval by organizing the transfer of neural information between the hippocampus and neocortex and within the hippocampal circuit (Hasselmo ; Siegle and Wilson ).…”

“…The physiological capacity to temporally coordinate dynamic neural activity within and between neural networks is believed to underlie normal cognitive processes (Fenton 2015;Barry et al 2016). Data supporting this theory largely stem from the demonstration that the temporal coordination of neuronal firing, with respect to theta oscillations within the hippocampal circuit (Mizuseki et al 2009), is correlated with learning and memory (Robbe and Buzsaki 2009;Douchamps et al 2013;Siegle and Wilson 2014;Barry et al 2016).…”