{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:55:27Z","timestamp":1793058927977,"version":"4.5.0"},"reference-count":263,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>The hippocampus-prefrontal cortex (HPC-PFC) pathway plays a fundamental role in executive and emotional functions. Neurophysiological studies have begun to unveil the dynamics of HPC-PFC interaction in both immediate demands and long-term adaptations. Disruptions in HPC-PFC functional connectivity can contribute to neuropsychiatric symptoms observed in mental illnesses and neurological conditions, such as schizophrenia, depression, anxiety disorders, and Alzheimer\u2019s disease. Given the role in functional and dysfunctional physiology, it is crucial to understand the mechanisms that modulate the dynamics of HPC-PFC communication. Two of the main mechanisms that regulate HPC-PFC interactions are synaptic plasticity and modulatory neurotransmission. Synaptic plasticity can be investigated inducing long-term potentiation or long-term depression, while spontaneous functional connectivity can be inferred by statistical dependencies between the local field potentials of both regions. In turn, several neurotransmitters, such as acetylcholine, dopamine, serotonin, noradrenaline, and endocannabinoids, can regulate the fine-tuning of HPC-PFC connectivity. Despite experimental evidence, the effects of neuromodulation on HPC-PFC neuronal dynamics from cellular to behavioral levels are not fully understood. The current literature lacks a review that focuses on the main neurotransmitter interactions with HPC-PFC activity. Here we reviewed studies showing the effects of the main neurotransmitter systems in long- and short-term HPC-PFC synaptic plasticity. We also looked for the neuromodulatory effects on HPC-PFC oscillatory coordination. Finally, we review the implications of HPC-PFC disruption in synaptic plasticity and functional connectivity on cognition and neuropsychiatric disorders. The comprehensive overview of these impairments could help better understand the role of neuromodulation in HPC-PFC communication and generate insights into the etiology and physiopathology of clinical conditions.<\/jats:p>","DOI":"10.3389\/fncel.2021.732360","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T04:02:10Z","timestamp":1633924930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":108,"title":["Neuromodulation of Hippocampal-Prefrontal Cortical Synaptic Plasticity and Functional Connectivity: Implications for Neuropsychiatric Disorders"],"prefix":"10.3389","volume":"15","author":[{"given":"Rafael Naime","family":"Ruggiero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Teixeira","family":"Rossignoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo Benette","family":"Marques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Monteiro","family":"de Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Neves","family":"Romcy-Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleiton","family":"Lopes-Aguiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pereira","family":"Leite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51972","article-title":"Spatiotemporal patterns of neocortical activity around hippocampal sharp-wave ripples.","volume":"9","author":"Abadchi","year":"2020","journal-title":"Elife"},{"key":"B2","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.neuron.2009.12.002","article-title":"Synchronized activity between the ventral hippocampus and the medial prefrontal cortex during anxiety.","volume":"65","author":"Adhikari","year":"2010","journal-title":"Neuron"},{"key":"B3","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/j.neuron.2011.07.027","article-title":"Single units in the medial prefrontal cortex with anxiety-related firing patterns are preferentially influenced by ventral hippocampal activity.","volume":"71","author":"Adhikari","year":"2011","journal-title":"Neuron"},{"key":"B4","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1177\/0269881115612239","article-title":"THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.","volume":"30","author":"Aguilar","year":"2016","journal-title":"J. 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