Perirhinal to prefrontal circuit in methamphetamine induced recognition memory deficits

Area of Science:

• Neuroscience
• Addiction Research
• Cognitive Psychology

Background:

• Chronic methamphetamine (meth) use leads to cognitive deficits and cortical dysfunction.
• Long-term meth self-administration in rats causes object recognition memory impairments linked to perirhinal cortex (PRH) plasticity.
• The PRH has extensive projections, including to the medial prefrontal cortex (mPFC), suggesting a potential role for this circuit in memory.

Purpose of the Study:

• To investigate the role of the reciprocal PRH-mPFC circuit in novel object recognition memory.
• To determine the directionality of information flow within the PRH-mPFC circuit during memory tasks.
• To assess the impact of manipulating PRH-mPFC circuit activity on meth-induced memory deficits.

Main Methods:

• Viral vectors (rgAAV) encoding GFP-tagged Cre recombinase were infused into the PRH or mPFC of rats.
• Rats were tested on novel object recognition tasks, exploring familiar and novel objects, or only familiar objects.
• GFP and Fos expression were analyzed in the mPFC and PRH; chemogenetic techniques were used to inhibit or activate the PRH-mPFC circuit.

Main Results:

• PRH neurons projecting to the mPFC were disproportionately activated by novel objects, indicating a PRH-to-mPFC communication flow.
• The percentage of Fos-positive cells in the PRH positively correlated with recognition memory performance.
• Chemogenetic inhibition of the PRH-mPFC circuit impaired object recognition memory, while activation reversed meth-induced deficits in previously dependent rats.

Conclusions:

• The PRH-to-mPFC pathway is critical for object recognition memory.
• Activating this circuit can ameliorate memory impairments associated with chronic methamphetamine use.
• These findings highlight a more complex neural circuitry underlying recognition memory than previously understood.