caa a22 4500 606201629 CHVBK 20210128100949.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00429-014-0880-z doi (NATIONALLICENCE)springer-10.1007/s00429-014-0880-z Limbic but not non-limbic kindling impairs conditioned fear and promotes plasticity of NPY and its Y2 receptor [Elektronische Daten] [J. Botterill, A. Guskjolen, W. Marks, H. Caruncho, L. Kalynchuk] Epileptic seizures negatively affect cognition. However, the mechanisms that contribute to cognitive impairments after seizures are largely unknown. Here, we examined the effects of long-term kindling (i.e., 99 stimulations) of limbic (basolateral amygdala, dorsal hippocampus) and non-limbic (caudate nucleus) brain sites on conditioned fear and hippocampal plasticity. We first showed that kindling had no effect on acquisition of a hippocampal-dependent trace fear-conditioning task but limbic kindling impaired the retrieval of these fear memories. To determine the relationship between memory and hippocampal neuronal activity, we examined the expression of Fos protein 90min after memory retrieval (i.e., 4days after the last kindling stimulation). We found that limbic kindling, but not non-limbic kindling, decreased Fos expression in the granule cell layer, hilus, CA3 pyramidal cell layer, and CA1 pyramidal cell layer. Next, to investigate a mechanism that could contribute to dampen hippocampal neuronal activity in limbic-kindled rats, we focused on the endogenous anticonvulsant neuropeptide Y (NPY), which is expressed in a subset of GABAergic interneurons and can prevent glutamate release through interactions with its Y2 receptor. We found that limbic kindling significantly decreased the number of NPY-immunoreactive cells in several hippocampal subfields despite minimal staining of the neurodegenerative marker Fluoro-Jade B. However, we also noted that limbic kindling enhanced NPY immunoreactivity throughout the mossy fiber pathway. In these same regions, we observed limbic kindling-induced de novo expression of the NPY Y2 receptor. These novel findings demonstrate the site-specific effects of kindling on cognition and NPY plasticity, and they provide evidence that altered hippocampal NPY after limbic seizures coincides with dampened neural activity and cognitive impairments. Springer-Verlag Berlin Heidelberg, 2014 Kindling nationallicence Amygdala nationallicence Hippocampus nationallicence Caudate nucleus nationallicence Fear conditioning nationallicence c-fos nationallicence NPY nationallicence Botterill J. Department of Psychology, University of Saskatchewan, S7N 5A5, Saskatoon, SK, Canada aut Guskjolen A. Department of Psychology, University of Saskatchewan, S7N 5A5, Saskatoon, SK, Canada aut Marks W. Department of Psychology, University of Saskatchewan, S7N 5A5, Saskatoon, SK, Canada aut Caruncho H. College of Pharmacy and Nutrition, University of Saskatchewan, S7N 5A5, Saskatoon, SK, Canada aut Kalynchuk L. Department of Medicine, University of Saskatchewan, 107 Wiggins Road, S7N 5E5, Saskatoon, SK, Canada aut Brain Structure and Function Springer Berlin Heidelberg 220/6(2015-11-01), 3641-3655 1863-2653 220:6<3641 2015 220 429 https://doi.org/10.1007/s00429-014-0880-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0880-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Botterill J. Department of Psychology, University of Saskatchewan, S7N 5A5, Saskatoon, SK, Canada aut NATIONALLICENCE 700 1- Guskjolen A. Department of Psychology, University of Saskatchewan, S7N 5A5, Saskatoon, SK, Canada aut NATIONALLICENCE 700 1- Marks W. Department of Psychology, University of Saskatchewan, S7N 5A5, Saskatoon, SK, Canada aut NATIONALLICENCE 700 1- Caruncho H. College of Pharmacy and Nutrition, University of Saskatchewan, S7N 5A5, Saskatoon, SK, Canada aut NATIONALLICENCE 700 1- Kalynchuk L. Department of Medicine, University of Saskatchewan, 107 Wiggins Road, S7N 5E5, Saskatoon, SK, Canada aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/6(2015-11-01), 3641-3655 1863-2653 220:6<3641 2015 220 429