The prefrontal cortex (PFC) plays a central role in cognitive functions such as decision-making and behavioral organization by integrating signals from cortical and subcortical regions. Its laminar structure is composed of superficial layers (I-III) that receive mediodorsal cortical and thalamic inputs, and deep layers (V-VI) that project to output regions such as the striatum and thalamus.
Abnormal activity in the PFC has been linked to psychiatric disorders such as schizophrenia and depression. Stress and drug addiction (e.g., alcohol, cocaine, psychedelics, cannabis) can also lead to a long-term modification of PFC activity.
Modulation of fEPSPs has been validated with reference compounds such as carbachol and serotonin. Indeed, the PFC receives serotonergic inputs primarily from the dorsal and median raphe nuclei. FTBMT, a selective GPR52 agonist known for its antipsychotic and cognition-enhancing properties also shows positive modulation of fEPSPs in PFC.
Multielectrode arrays enable hours-stable recordings of postsynaptic responses in both the superficial (layers I–III) and deep layers (V–VI) of the prefrontal cortex which is particularly valuable for target validation, pharmacological profiling, and neuropsychiatric drug discovery.
Illustration of the recording area targeting layer V or layer II-III of the mPFC
A. Schematics depicting the mPFC localization and the area targeted for recordings delineated by the red dotted line.
B. Picture showing the MEA electrode positioning
ACC: anterior cingulate cortex; PrL: prelimbic cortex; IL: infralimbic cortex; M1-M2: motor cortex; fmi: forceps minor (white matter)
CPu: caudate putamen (striatum).
References
Nishiyama K, Suzuki H, Harasawa T, Suzuki N, Kurimoto E, Kawai T, Maruyama M, Komatsu H, Sakuma K, Shimizu Y, Shimojo M. FTBMT, a Novel and Selective GPR52 Agonist, Demonstrates Antipsychotic-Like and Procognitive Effects in Rodents, Revealing a Potential Therapeutic Agent for Schizophrenia. J Pharmacol Exp Ther. 2017 Nov;363(2):253-264. doi: 10.1124/jpet.117.242925. Epub 2017 Aug 29. PMID: 28851764.
Sargin D, Jeoung HS, Goodfellow NM, Lambe EK. Serotonin Regulation of the Prefrontal Cortex: Cognitive Relevance and the Impact of Developmental Perturbation. ACS Chem Neurosci. 2019 Jul 17;10(7):3078-3093. doi: 10.1021/acschemneuro.9b00073. Epub 2019 Jul 1. PMID: 31259523.
