Early life seizures cause long-standing impairment of the hippocampal map.
Children with seizures are at risk for long-term cognitive deficits. Similarly, recurrent seizures in developing rats are associated with deficits in spatial learning and memory. However, the pathophysiological bases for these deficits are not known. Hippocampal place cells, cells that are activated selectively when an animal moves through a particular location in space, provides the animal with a spatial map. We hypothesized that seizure-induced impairment in spatial learning is a consequence of the rat's inability to form accurate and stable hippocampal maps. To directly address the cellular concomitants of spatial memory impairment, we recorded the activity of place cells from hippocampal subfield CA1 in freely moving rats subjected to 100 brief flurothyl-induced seizures during the first weeks of life and then tested them in the Morris water maze and radial-arm water maze followed by place cell testing. Compared to controls, rats with recurrent seizures had marked impairment in Morris water maze and radial-arm water maze. In parallel, there were substantial deficits in action potential firing characteristics of place cells with two major defects: i) the coherence, information content, center firing rate, and field size were reduced compared to control cells; and ii) the fields were less stable than those in control place cells. These results show that recurrent seizures during early development are associated with significant impairment in spatial learning and that these deficits are paralleled by deficits in the hippocampal map. This study thus provides a cellular correlate for how recurrent seizures during early development lead to cognitive impairment.
Karnam
Havisha B
HB
Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, NH 03756, USA.
Zhou
Jun-Li
JL
Huang
Li-Tung
LT
Zhao
Qian
Q
Shatskikh
Tatiana
T
Holmes
Gregory L
GL
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D001931:Brain Mapping / Q000379:methods; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology*; D003292:Convulsants; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D005481:Flurothyl; D006624:Hippocampus / Q000254:growth & development / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D009949:Orientation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000502:physiology*; D013995:Time
D003292:Convulsants; D005481:Flurothyl