The PTZ kindling mouse model of epilepsy exhibits exploratory drive deficits and aberrant activity amongst VTA dopamine neurons in both familiar and novel space

Behavioural Brain Research
Mahboubeh AhmadiBechara J Saab

Abstract

Recurrent seizures that define epilepsy are often accompanied by psychosocial problems and cognitive deficits with incompletely understood aetiology. We therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to examine potential seizure-associated neuropathologies, focusing on motivation, memory and novel-environment-induced activation of midbrain dopaminergic neurons. In addition to recurrent seizures, we found that PTZ kindling led to a strong suppression of novelty-driven exploration while largely sparing fear-driven exploration. The deficits in exploratory drive may be relevant for other cognitive impairments since reduced unassisted rearing in a learning arena correlated with poorer spatial memory of object location. Using c-Fos immunofluorescence as a marker of neuronal activity, we observed that dopamine neurons within the ventral tegmental area (VTA) of PTZ kindled mice demonstrate hyperactivity at baseline and hypoactivity in response to a novel environment compared to saline-injected cagemate controls. These data extend previous findings of PTZ kindling-mediated disruptions of hippocampal processes important for novel environment recognition and learning by demonstrating PTZ kindling also induce...Continue Reading

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Oct 28, 2016·Behavioural Brain Research·Alejandro Tsai CabalBechara J Saab

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Citations

Aug 3, 2017·Journal of Neural Transmission·J Vuong, Annaelle Devergnas
Dec 2, 2020·Life Sciences·Enes AkyuzYam Nath Paudel
Aug 28, 2021·International Journal of Molecular Sciences·Xiaoyu JiJie Wu

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