Journal Article

DZNE-2020-05459

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination.

Minge, D. ; Senkov, O.DZNE* ; Kaushik, R.DZNE* ; Herde, M. K. ; Tikhobrazova, O. ; Wulff, A. B. ; Mironov, A. ; van Kuppevelt, T. H. ; Oosterhof, A. ; Kochlamazashvili, G. ; Dityatev, A.DZNE* ; Henneberger, C. (Last author)DZNE*

2017
Oxford Univ. Press Oxford

This record in other databases:    

Please use a persistent id in citations: doi:10.1093/cercor/bhx003

Abstract: Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3-CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca2+ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning.

Keyword(s): Animals (MeSH) ; Ankyrins: biosynthesis (MeSH) ; Ankyrins: genetics (MeSH) ; CA1 Region, Hippocampal: cytology (MeSH) ; CA1 Region, Hippocampal: physiology (MeSH) ; CA3 Region, Hippocampal: cytology (MeSH) ; CA3 Region, Hippocampal: physiology (MeSH) ; Calcium Signaling: physiology (MeSH) ; Conditioning, Psychological (MeSH) ; Discrimination, Psychological: physiology (MeSH) ; Fear: physiology (MeSH) ; Heparin Lyase: pharmacology (MeSH) ; Heparitin Sulfate: physiology (MeSH) ; In Vitro Techniques (MeSH) ; Long-Term Potentiation: physiology (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Nerve Net: physiology (MeSH) ; Neuronal Plasticity: physiology (MeSH) ; Pyramidal Cells: physiology (MeSH) ; Synapses: physiology (MeSH) ; Theta Rhythm (MeSH) ; Ank3 protein, mouse ; Ankyrins ; Heparitin Sulfate ; Heparin Lyase

---

Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)
2. U Preclinical Researchers - Bonn (U Preclinical Researchers - Bonn)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2017

---

Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

---