K.A.C. Elliott 2019 Lecture: The reciprocal GABAergic septo-hippocampal connection: target selectivity and function


Montreal Neurological Institute Jeanne Timmins Ampthitheatre, 3801 rue University, Montreal, QC, H3A 2B4, CA

Speaker: Dr. Tamás F. Freund
Institute of Experimental Medicine
Hungarian Academy of Sciences
Budapest, Hungary

Abstract: Subcortical pathways that carry information about motivation, emotions and the autonomic state of the animal can efficiently influence cortical EEG patterns, and thereby modulate learning and memory processes, selective attention, arousal and mood. This lecture will shed light on the neuronal network mechanisms underlying such a powerful control mechanism taking the septohippocampal system as an example. Anatomical and electrophysiological studies of the past decades demonstrate that a reciprocal GABAergic connection exists between the medial septum (MS) and the hippocampus, and the former region likely contains the pacemaker neurons of hippocampal theta activity. In addition to reviewing earlier work on how rhythmic disinhibition can induce theta oscillation in the hippocampus, recent results will be presented on the cholinergic septohippocampal pathway, and the GABAergic feedback from the hippocampus to the medial septal pacemaker circuitry. Selective optogenetic stimulation of cholinergic septohippocampal neurons diminished sharp wave ripples in the hippocampus, and paved the way to theta generation. Selective manipulation of the somatostatin-expressing hippocampo-septal (HS) fibers with a similar optogenetic approach, and recording of the response of medial septal neurons both in urethane-anesthetized and in freely behaving mice showed that activation of the HS feedback robustly altered the firing of MS neurons during spontaneuous theta or non-theta in urethane, as well as activity associated to REM-like states. In contrast, theta bursting discharge patterns coupled to evoked theta in urethane and exploratory theta in freely behaving mice was not affected by stimulating the HS connection. These results shed new light on the role of the reciprocal inhibitory circuitry in generating theta oscillations.

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This named lecture honors the legacy of Dr. KAC Elliot, the first neurochemist at The Neuro.  Dr. Elliot contributed immensely to the understanding of the basic chemical mechanisms of cerebral edema, epilepsy, and brain tumours.  In a landmark paper in 1957, Dr. Elliot and his colleagues identified the role of gamma-aminobutyric acid (GABA), now believed to be the major inhibitory transmitter in the brain.

Tamás F. Freund

Tamás F. Freund is a Professor and Director of the Institute of Experimental Medicine, Hungarian Academy of Sciences, and Chairman of the Neuroscience Department, Péter Pázmány Catholic University in Budapest. He graduated as a biologist at the Eötvös University in Budapest in 1983. He has been president of the Federation of European Neuroscience Soceities (FENS) from 2004 till 2006, and Chairman of the IBRO Central and Eastern Europe Regional Committee (1999-2003). He is a member of the Hungarian Academy of Sciences (1998, vicepresident since 2014), the Academia Europaea (London, 2000), the German Academy of Sciences Leopoldina (2001), the Academia Scientiarum et Artium Europaea (2001), and the American Academy of Arts and Sciences (2014). The major awards he received include the KRIEG Cortical Discoverer Award and the Cajal Medal (1998, U.S.A.), the Bolyai Prize (2000, Hungary), the Széchenyi Prize, (2005), The Brain Prize (2011, Denmark), and the Prima Primissima award (2013).

His main achievements include the discovery of new molecular pathways in nerve cell communication, identity and principles of neuron connectivity that builds up cortical circuitry, and generation of network activity patterns that underlie various stages of information processing and storage in the brain. Made significant discoveries regarding structure and function of cortical microcircuits, with particular attention to their inhibitory components and their relationship to oscillations that underlie different stages of memory formation. Discovered that pacemaker neurons in the septal region are GABAergic (inhibitory) and selectively innervate GABAergic interneurons in the hippocampus, thereby synchronizing activity rhythmically at theta frequency. Results in epilepsy field provided direct evidence that early loss of inhibitory interneurons lead to conditions that allow interictal spiking to generate hyperexcitable circuits and ultimately lead to the chronic phase characterized by spontaneous seizures. With his research group, discovered that CB1 cannabinoid receptors inhibit neurotransmitter release, and described the structure and operational principles of this circuit breaker in several brain regions.