Synaptic biomarker reduction and impaired cognition in the sub-chronic PCP mouse model for schizophrenia

Background: Sub-chronic phencyclidine treatment (scPCP) provides a translational rat model for cognitive impairments associated with schizophrenia (CIAS). CIAS genetic risk factors may be more easily studied in mice; however, CIAS associated biomarker changes are relatively unstudied in the scPCP mouse. Aim: To characterize deficits in object recognition memory and synaptic markers in frontal cortex and hippocampus of the scPCP mouse. Methods: Female c57/bl6 mice received 10 daily injections of PCP (scPCP; 10 mg/kg, s.c.) or vehicle ( n = 8/group). Mice were tested for novel object recognition memory after either remaining in the arena (‘no distraction’) or being removed to a holding cage (‘distraction’) during the inter-trial interval. Expression changes for parvalbumin (PV), glutamic acid decarboxylase (GAD67), synaptosomal-associated protein 25 (SNAP-25) and postsynaptic density 95 (PDS95) were measured in frontal cortex, dorsal and ventral hippocampus. Results: scPCP mice showed object memory deficits when distracted by removal from the arena, where they treated previously experienced objects as novel at test. scPCP significantly reduced PV expression in all regions and lower PSD95 levels in frontal cortex and ventral hippocampus. Levels of GAD67 and SNAP-25 were unchanged. Conclusions: We show for the first time that scPCP mice: (a) can encode and retain object information, but that this memory is susceptible to distraction; (b) display amnesia after distraction; and (c) express reduced PV and PSD95 in frontal cortex and hippocampus. These data further support reductions in PV-dependent synaptic inhibition and NMDAR-dependent glutamatergic plasticity in CIAS and highlight the translational significance of the scPCP mouse.

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Crossed unilateral lesions of medial forebrain bundle and either inferior temporal or frontal cortex impair object recognition memory in Rhesus monkeys

Behavioural Brain Research ◽

10.1016/s0166-4328(00)00384-3 ◽

2001 ◽

Vol 121 (1-2) ◽

pp. 1-10 ◽

Cited By ~ 20

Author(s):

Alexander Easton ◽

Amanda Parker ◽

David Gaffan

Keyword(s):

Object Recognition ◽

Recognition Memory ◽

Frontal Cortex ◽

Rhesus Monkeys ◽

Medial Forebrain Bundle ◽

Object Recognition Memory

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Chemogenetic silencing of hippocampus and amygdala reveals a double dissociation in periadolescent obesogenic diet-induced memory alterations

10.1101/2020.07.20.212258 ◽

2020 ◽

Cited By ~ 1

Author(s):

Fabien Naneix ◽

Ioannis Bakoyiannis ◽

Marianela Santoyo-Zedillo ◽

Clémentine Bosch-Bouju ◽

Gustavo Pacheco-Lopez ◽

...

Keyword(s):

Object Recognition ◽

Recognition Memory ◽

Basolateral Amygdala ◽

Memory Deficits ◽

Ventral Hippocampus ◽

Brain Regions ◽

Obesity Prevalence ◽

Odor Aversion ◽

Object Recognition Memory

1ABSTRACTIn addition to numerous metabolic comorbidities, obesity is associated with several adverse neurobiological outcomes, especially learning and memory alterations. Obesity prevalence is rising dramatically in youth and is persisting in adulthood. This is especially worrying since adolescence is a crucial period for the maturation of certain brain regions playing a central role in memory processes such as the hippocampus and the amygdala. We previously showed that periadolescent exposure to obesogenic high-fat diet (HFD) had opposite effects on hippocampus- and amygdala-dependent memory, impairing the former and enhancing the latter. However, the causal role of these two brain regions in periadolescent HFD-induced memory alterations remains unclear. Here, we first showed that periadolescent HFD induced long-term, but not short-term, object recognition memory deficits, specifically when rats were exposed to a novel context. Using chemogenetic approaches to inhibit targeted brain regions, we then demonstrated that recognition memory deficits are dependent on the activity of the ventral hippocampus, but not the basolateral amygdala. On the contrary, the HFD-induced enhancement of conditioned odor aversion requires specifically amygdala activity. Taken together, these findings suggest that HFD consumption throughout adolescence impairs long-term object recognition memory through the overactivation of the ventral hippocampus during memory acquisition. Moreover, these results further highlight the bidirectional effects of adolescent HFD on hippocampal and amygdala functions.

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