GABAergic parvalbumin-expressing interneurons play a role in memory impairment in rat models of Parkinson's disease

Abstract

We investigated the role of hippocampal GABAergic parvalbumin-expressing (PV) interneurons in spatial and hippocampus-dependent memory abilities in rat models of Parkinson's disease (PD). Experiments were performed in adult male Wistar rats, including physiological controls (n=14) and toxin lesion-induced PD models: PD cholinopathy (n=10), hemiparkinsonism (n=7), and hemiparkinsonism with PD cholinopathy (n=6). Behavioral assessments and PV immunohistochemistry were performed 14 and 42 days after lesions. Spatial habituation test and novel object recognition test were used to assess spatial and hippocampus-dependent short- and long-term recognition memory. All experimental groups had no motor impairments during the follow-up period (X2 ≥2.01, p≥0.07). Although hippocampal PV expression remained unchanged over time in PD cholinopathy (z≥-1.91, p≥0.06), we evidenced impairments in spatial, short- and long-term recognition memory, but only at day 42 (X2 ≥0.38, p=0.83; t=0.13, p=0.91). In the hemiparkinsonian rats, unchanged hippocampal PV expression (z≥-1.52, p≥0.14) was followed by impairment in spatial memory (X2 ≥2.87, p≥0.22), but both recognition memories were intact over time (t≥3.16, p≤0.03). In the hemiparkinsonian rats with PD cholinopathy, long-lasting impairment of spatial memory (X2 ≥0.72, p≥0.22) was followed by delayed short- and long-term impairment of recognition memory (t=-0.24, p=0.82) along with hippocampal PV suppression (z=-3.17, p=10-3), which was functionally coupled to impairment of recognition memory (r=0.52, p=0.04). Our results suggest that dopaminergic denervation plays an important role in impairing spatial memory in the prodromal stage of PD, whereas cholinergic denervation and hippocampal PV suppression impair short- and long-term memory in a delayed manner in PD cholinopathy and hemiparkinsonism with PD cholinopathy.