Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze

Abstract

Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS. Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. In agreement with this hypothesis, serotonin depletion in the SUMn/PHn results in deficient spatial learning and alterations in CA1 theta activity-related learning in a Morris water maze. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory. We infused 5,7-DHT bilaterally into the SUMn in rats and evaluated place learning in the standard Morris water maze task. Hippocampal (CA1 and dentate gyrus), septal and SUMn EEG were recorded during training of the test. The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results provide evidence in support of a role for serotonin as a modulator of hippocampal learning, acting through changes in the synchronicity evoked in several relays of the SAS.

A Critical Assessment of Directed Connectivity Estimates with Artificially Imposed Causality in the Supramammillary-Septo-Hippocampal Circuit

“…The present data suggest that this partial rescue is likely to be independent of HPCxSuM theta coherence, given coherence/PPC in the REG condition is statistically indistinguishable from TET and IRR and much lower than CON and BP. Additionally, SuM theta PSD was also found to be uncoupled to water maze learning (i.e., lowest in REG and equivalent to CON in TET and IRR), suggesting water maze learning may also be relatively independent of SuM theta oscillations, despite reported experience-dependent changes (Ruan et al, 2011 ; Hernandez-Perez et al, 2015 ). While SuM inactivation moderately impairs water maze learning in single-day (Pan and McNaughton, 1997 ) or multi-day (Shahidi et al, 2004 ) versions of the task, lesion of SuM does not appear to affect water maze learning in the multi-day version of the task (Pan and McNaughton, 2002 ; Aranda et al, 2006 ).…”

“…However, it has been shown that SuM integrity is not always necessary for HPC theta to occur (Thinschmidt et al, 1995 ) and may merely reduce peak frequency in the freely moving rat (McNaughton et al, 1995 ). More recent data based on spike-field Granger causality have suggested a role for the SuM in modulating HPC theta at higher frequencies (Kocsis and Kaminski, 2006 ), which is related to water maze learning/performance (McNaughton et al, 2006 ; Ruan et al, 2011 ; Hernandez-Perez et al, 2015 ).…”

Traditional Chinese Medicine Huannao Yicong Decoction Extract Decreases Tau Hyperphosphorylation in the Brain of Alzheimer’s Disease Model Rats Induced by Aβ1–42

“…Morris water maze (DMS-2 type, produced by the Institute of Materia Medica, Chinese Academy of Medical Sciences) was used before and after drug treatment to detect changes in cognitive function [6]. The test consisted of two parts: a place navigation and spatial probe test.…”

Medial entorhinal cortex activates in a traveling wave

“…Theta is well understood both in terms of its underlying physiology and its potential function (for reviews, see Buzsáki, 2002;Dickson et al, 2000;Vinogradova, 1995). Functionally, theta is attributed with supporting navigation (Blair et al, 2007;Brandon et al, 2011;Burgess et al, 2007;Newman and Hasselmo, 2014;Onslow et al, 2014), mediating associational learning (Caplan et al, 2003;Hasselmo et al, 2002;Hernández-Pérez et al, 2015;2016;Honey et al, 2017;Muller et al, 2018;Norman et al, 2006;Patel et al, 2012), and pacing the relative timing of the distinct components of the entorhinal-hippocampal circuit (Mizuseki et al, 2009). These proposed functions are not mutually exclusive.…”