I am presenting a poster at the Society for Neuroscience (SfN) meeting in San Diego, in November 3, 13:00-17:00.
D. APŠVALKA, M. C. ANDERSON. Controlling unwanted memories: The medial septal pacemaker suppression hypothesis.
The ability to control unwanted thoughts and memories is essential to mental health and wellbeing. Prior research has found that stopping intrusive memories involves top-down control by the prefrontal cortex and subsequent inhibition of hippocampal retrieval processes. Moreover, the efficacy of this fronto-hippocampal inhibitory pathway depends on hippocampal GABA to enable memory suppression. Specifically, higher resting concentration of hippocampal GABA has predicted better mnemonic control.
These findings raise questions about the mechanisms through which hippocampal GABA enables the suppression of unwanted memories. The prefrontal cortex itself does not have direct connections to the hippocampus. Therefore, the question is, what is acting on the GABAergic interneurons in the hippocampus during memory suppression? Animal research shows that the medial-septal nucleus in the basal forebrain acts as a pacemaker for hippocampal theta oscillations necessary for memory encoding and retrieval. A pathway linking the medial-septal nucleus to the hippocampus involves GABAergic projections that terminate on hippocampal GABAergic interneurons, suppressing them and disinhibiting the hippocampus. We hypothesise that if the medial-septal nucleus itself were suppressed, it would truncate the inhibitory input to hippocampal GABAergic interneurons, raising hippocampal tonic inhibition. Subsequently, this may disrupt memory retrieval.
To investigate the medial-septal pacemaker suppression hypothesis, we hand traced the medial-septal nucleus in 330 participants in our fMRI studies of the Think/No-Think task. 103 of these participants had also provided intrusion ratings during the No-Think trials, reporting whether the unwanted memory intruded into their minds.
The results provide strong evidence for the medial-septal nucleus suppression during No-Think compared to Think trials (d = 0.339, p = 2.55 x 10-10), and especially during intrusion compared to no-intrusion trials (d = 0.378, p = 2.19 x 10-4). In ongoing work, we are investigating the interactions between the prefrontal cortex, medial-septal nucleus, and hippocampus during retrieval suppression; specificity of the medial-septal nucleus, compared to other basal forebrain structures; and resting-state functional connectivity between the medial-septal nucleus and other brain regions.
The current findings provide strong initial support for the medial-septal pacemaker suppression hypothesis. Specifically, when stopping intrusive memories, activity in the medial-septal nucleus is suppressed, potentially causing hippocampal tonic inhibition and disabling the memory recall.