PhD Scientific Days 2020

Molecular Sciences I. Posters

Cell Type-specific Examination of Tonic Cannabinoid Signaling

Előadó neve

Barti, Benjamin, MSc

Előadó munkahelye

Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine

Előadó telefonszáma

0036705828829

Előadó e-mail címe

barti.benjamin@koki.mta.hu

Az előadás címe

Cell Type-specific Examination of Tonic Cannabinoid Signaling

Szerző(k) neve és munkahelye

Benjamin Barti1, 2, Kata Kenesei1, Marco Ledri1, 3, Blanka Tóth4, Vivien Miczán1, 5, George Horvai4, and István Katona1
1) Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Budapest, Hungary;
2) Szentágothai János Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary;
3) Epilepsy Center, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden;
4) Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics;
5) Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary;

Szekció

Molecular Sciences I. Posters

Language of the presentation

Hungarian

Section, first choice

Neurosciences

Section, second choice

Molecular Sciences

Összefoglaló szövege

Retrograde endocannabinoid (eCB) signaling via presynaptic cannabinoid (CB1) receptors play an essential part in the calibration of neurotransmitter release probability in both phasic and tonic manner. Tonic eCB signaling plays considerable role in fine-tuning synaptic strength and thus adjusting network oscillations in interneuron type-specific and activity-dependent manner. Specific disruption of this pathway is associated with many neurological disorders, such as autism, epileptic seizures and Huntington’s disease indicating its significant importance. However, despite the fact, that the most common endocannabinoid messenger 2-arachidonoylglycerol (2-AG) and its predominant synthesizing enzyme diacylglycerol lipase-α (DGLα) are essential elements of phasic eCB signaling, they role in persistent eCB signaling has remained elusive. Therefore, we aimed to study specific features of this molecular pathway in cell-type specific manner using paired patch-clamp electrophysiology with the combination of Stochastic Optical Reconstruction Microscopy (STORM), and liquid chromatography/tandem mass spectrometry. We found that presynaptic CB1 receptors on hippocampal perisomatic interneuron axon terminals specifically mediate tonic eCB signaling and AM251 is a specific antagonist/invers-agonist of the CB1 receptors. Furthermore, we have shown the presence of a persistently active 2-AG production in the slice preparations mediated by DGLα enzyme. The continuously generated 2-AG is kept under the tight control of the main 2-AG hydrolyzing enzyme monoacylglycerol lipase (MGL), although surprisingly, the lack of tonic 2-AG production does not alter basic synaptic transmission. Moreover, despite the significant role of DGLα in neural pathfinding and synaptogenesis, no morphological alterations were observed at perisomatic interneurons in mice lacking DGLα. Our findings uncovered a previously undescribed, DGLα – 2-AG independent form of tonic eCB signaling at these synapses. This signaling pathway is able to maintain synaptic function on homeostatic levels even in the absence of DGLα.

Additional Information

István Katona
istvan.katona@koki.mta.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4747

Start

11:23

End

11:26

Authors (legacy)

Benjamin Barti1, 2, Kata Kenesei1, Marco Ledri1, 3, Blanka Tóth4, Vivien Miczán1, 5, George Horvai4, and István Katona1
1) Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Budapest, Hungary;
2) Szentágothai János Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary;
3) Epilepsy Center, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden;
4) Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics;
5) Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary;