ABSTRACT
Here we describe a novel mouse model of temporal lobe epilepsy (TLE) that moves the site of kainate injection from the rodent dorsal hippocampus (corresponding to the human posterior hippocampus) to the ventral hippocampus (corresponding to the human anterior hippocampus). We compare the phenotypes of this new model-with respect to seizures, cognitive impairment, affective deficits, and histopathology-to the standard dorsal intrahippocampal kainate model. Our results demonstrate that histopathological measures of granule cell dispersion and mossy fiber sprouting maximize near the site of kainate injection. Somewhat surprisingly, both the dorsal and ventral models exhibit similar spatial memory impairments in addition to similar electrographic and behavioral seizure burdens. In contrast, we find a more pronounced affective (anhedonic) phenotype specifically in the ventral model. These results demonstrate that the ventral intrahippocampal kainic acid model recapitulates critical pathologies of the dorsal model while providing a means to further study affective phenotypes such as depression in TLE.
Subject(s)
Anhedonia , Anxiety , Behavior, Animal , Cognitive Dysfunction , Disease Models, Animal , Epilepsy, Temporal Lobe , Excitatory Amino Acid Agonists/pharmacology , Hippocampus/drug effects , Kainic Acid/pharmacology , Anhedonia/drug effects , Anhedonia/physiology , Animals , Anxiety/chemically induced , Anxiety/etiology , Anxiety/physiopathology , Behavior, Animal/drug effects , Behavior, Animal/physiology , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Dentate Gyrus/drug effects , Electroencephalography , Epilepsy, Temporal Lobe/chemically induced , Epilepsy, Temporal Lobe/complications , Epilepsy, Temporal Lobe/physiopathology , Excitatory Amino Acid Agonists/administration & dosage , Female , Humans , Kainic Acid/administration & dosage , Male , Maze Learning/drug effects , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Mossy Fibers, Hippocampal/drug effectsABSTRACT
Early detection of Alzheimer's disease (AD) raises a number of challenging legal questions. In this essay, we explore some of those questions, such as: Is a neurological indicator of increased risk for AD a legally relevant brain state before there are any outward behavioral manifestations? How should courts address evidentiary challenges to the admissibility of AD-related neuroimaging? How should the government regulate the marketing of neuroimaging diagnostic tools? How should insurance coverage for the use of these new tools be optimized? We suggest that many voices and multidisciplinary perspectives are needed to answer these questions and ensure that legal responses are swift, efficient, and equitable.
