Deep Brain Stimulation of the dorsal raphe abolishes serotonin 1A facilitation of AMPA receptor-mediated synaptic currents in the ventral hippocampus

• Published in: Behavioural brain research Vol. 403; p. 113134
• Main Authors: Viana, M.B., Martins, R.S., Silva, M.S.C.F., Xapelli, S., Vaz, S.H., Sebastião, A.M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 09.04.2021
• Subjects: 5-HT1A receptors; Age Factors; Animals; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - metabolism; CA1 Region, Hippocampal - physiology; Deep Brain Stimulation; Dorsal Raphe Nucleus; Dorsal region of the dorsal raphe; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Excitatory synaptic transmission; Hippocampus; Male; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A - drug effects; Receptor, Serotonin, 5-HT1A - metabolism; Receptors, AMPA - metabolism; Serotonergic signaling; Serotonin 5-HT1 Receptor Agonists - pharmacology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Excitatory synaptic transmission; 5-HT1A receptors; Serotonergic signaling; Dorsal region of the dorsal raphe; Hippocampus; Deep Brain Stimulation
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2021.113134

•Changes in 5-HT1A receptor-mediated hippocampal synaptic transmission occur with age.•These changes lead to a facilitatory effect of 5-HT1A receptors.•Deep Brain Stimulation blocks this serotonergic facilitatory action. In a previous study we showed that Deep Brain Stimulation (DBS) of the rat dorsal subregion of the dorsal raphe (DRD), which sends serotonergic projections to forebrain areas, such as the ventral hippocampus, induces anxiolytic-like effects. The purpose of the present study was to investigate neurobiological alterations which might underline these behavioral effects. For that, we tested the influence of DBS upon the neuromodulatory action of serotonin on excitatory post-synaptic currents (EPSCs) in the ventral hippocampus. Male Wistar rats were submitted to high-frequency stimulation (100 μA, 100 Hz) of the DRD for 1 h during three consecutive days. On the third day, immediately after the DBS procedure, animals were euthanized. Slices of the ventral hippocampus were processed for whole cell patch clamp recordings of AMPA-receptor (AMPAR) mediated EPSCs in the CA1 area. As reported by others, we confirmed that in pre-weaning rats a high affinity 5-HT1A receptor agonist (8-OH-PIPAT, 0.5−5nM) inhibits EPSCs. However, in adult rats (non-operated or sham-operated), 8-OH-PIPAT (0.5−5 nM) increased EPSC amplitude, an effect blocked by the 5-HT1A antagonist WAY-100,635 (200 nM). Importantly, in adult rats exposed to DBS, the 5-HT1A agonist was devoid of effect. Taken together these results show that: 1) changes in 5-HT1A receptor-mediated hippocampal synaptic transmission occur with age; 2) these changes lead to a facilitatory effect of 5-HT1A receptors; 3) DBS blocks this serotonergic facilitatory action. These observations suggest that an alteration in serotonin modulation of limbic areas may underlie the psychotherapeutic effects of DBS.