Cognitive performance in aged rats is associated with differences in distinctive neuronal populations in the ventral tegmental area and altered synaptic plasticity in the hippocampus

Introduction: Deterioration of cognitive functions is commonly associated with
aging, although there is wide variation in the onset and manifestation. Albeit
heterogeneity in age-related cognitive decline has been studied at the cellular
and molecular level, there is poor evidence for electrophysiological correlates.
The aim of the current study was to address the electrophysiological basis of
heterogeneity of cognitive functions in cognitively Inferior and Superior old (19-
20 months) rats in the ventral tegmental area (VTA) and the hippocampus, having
Young (12 weeks) rats as a control. The midbrain VTA operates as a hub amidst
affective and cognitive facets, processing sensory inputs related to motivated
behaviours and hippocampal memory. Increasing evidence shows direct
dopaminergic and non-dopaminergic input from the VTA to the hippocampus.
Methods: Aged Superior and Inferior male rats were selected from a cohort
of 88 animals based on their performance in a spatial learning and memory
task. Using in vivo single-cell recording in the VTA, we examined the electrical
activity of different neuronal populations (putative dopaminergic, glutamatergic
and GABAergic neurons). In the same animals, basal synaptic transmission and
synaptic plasticity were examined in hippocampal slices.
Results: Electrophysiological recordings from the VTA and hippocampus showed
alterations associated with aging per se, together with differences specifically
linked to the cognitive status of aged animals. In particular, the bursting activity of
dopamine neurons was lower, while the firing frequency of glutamatergic neurons
was higher in VTA of Inferior old rats. The response to high-frequency stimulation in
hippocampal slices also discriminated between Superior and Inferior aged animals.
Discussion: This study provides new insight into electrophysiological
information underlying compromised cerebral ageing. Further understanding of brain senescence, possibly related to neurocognitive decline,
will help develop new strategies towards the preservation of a high quality
of life.