Temperature is a fundamental property that affects all biologic systems, including the brain. The high temperatures of fever states can trigger febrile seizures in children, yet little is known about the effects of hyperthermic temperatures on the excitability of the immature nervous system. Febrile seizures cause long-term cellular and molecular changes in the hippocampus. However, acute effects of hyperthermia on hippocampal neurons have not been studied. My project was motivated by the need to understand the effects of hyperthermia and the mechanisms of febrile seizures. I studied the effects of hyperthermic temperatures on the physiology of neurons, synapses, and circuits in the juvenile mouse hippocampus. My central hypothesis is that febrile seizures arise from substantial hyperthermia-induced excitation. I found that hyperthermia increased the excitability of all principal cells in the hippocampus. However CA3 pyramidal cells were significantly more responsive than either CA1 pyramidal cells or the granule cells of the dentate gyrus (Chapter 2). Changes in synaptic inhibition are common causes of seizure generation. I examined the effects of hyperthermia on a major class of hippocampal inhibitory cell, the O-LM interneurons (identified by their green fluorescent protein expression in a transgenic mouse line). O-LM interneurons were strongly excited by heat, and CA3 O-LM cells were more responsive than those in CA1 (Chapter 3). Although all proteins are affected by temperature, some types--including the heat-activated TRPV1 channels--are particularly sensitive and may play an important role in brain function (Gibson et al., 2008). I tested whether TRPV1 channels influence febrile seizure susceptibility. The absence of TRPV1 channels increased the temperature threshold for behavioral hyperthermic seizures and reduced heat-activated multiunit activity in hippocampus in vitro (Chapter 4). My results demonstrate that hyperthermic temperatures increase the excitability of all major classes of hippocampal neurons, and suggest that heat-sensitive TRPV1 channels may modulate the threshold for febrile seizures.
Kim, Jennifer A.,
"Febrile Seizures, Hyperthermia and Hippocampal Neuron Physiology"
(2010).
Neuroscience Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0JD4V01
