Dentate Gyrus Local Circuit is Implicated in Learning Under Stress—a Role for Neurofascin

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• 作者：Femke M. P. Zitman ; Morgan Lucas ; Sabine Trinks…
• 关键词：Axon initial segment (AIS) ; Hippocampus ; GABAA receptor clustering ; Learning impairment
• 刊名：Molecular Neurobiology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：53
• 期：2
• 页码：842-850
• 全文大小：1,414 KB
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• 作者单位：Femke M. P. Zitman (1)
  Morgan Lucas (1)
  Sabine Trinks (3)
  Laura Grosse-Ophoff (1)
  Martin Kriebel (3)
  Hansjürgen Volkmer (3)
  Gal Richter-Levin (1) (2) (4)
  
  1. “Sagol” Department of Neurobiology, University of Haifa, Mount Carmel, 31095, Haifa, Israel
  3. Department of Molecular Biology, Natural and Medical Sciences Institute (NMI), Universität Tübingen, Markwiesenstr. 55, 72770, Reutlingen, Germany
  2. Department of Psychology, University of Haifa, Mount Carmel, 31905, Haifa, Israel
  4. The Institute for the Study of Affective Neuroscience (ISAN), Department of Psychology, University of Haifa, Mount Carmel, 31905, Haifa, Israel
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

The inhibitory synapses at the axon initial segment (AIS) of dentate gyrus granular cells are almost exclusively innervated by the axo-axonic chandelier interneurons. However, the role of chandelier neurons in local circuitry is poorly understood and controversially discussed. The cell adhesion molecule neurofascin is specifically expressed at the AIS. It is crucially required for the stabilization of axo-axonic synapses. Knockdown of neurofascin is therefore a convenient tool to interfere with chandelier input at the AIS of granular neurons of the dentate gyrus. In the current study, feedback and feedforward inhibition of granule cells was measured in the dentate gyrus after knockdown of neurofascin and concomitant reduction of axo-axonic input. Results show increased feedback inhibition as a result of neurofascin knockdown, while feedforward inhibition remained unaffected. This suggests that chandelier neurons are predominantly involved in feedback inhibition. Neurofascin knockdown rats also exhibited impaired learning under stress in the two-way shuttle avoidance task. Remarkably, this learning impairment was not accompanied by differences in electrophysiological measurements of dentate gyrus LTP. This indicates that the local circuit may be involved in (certain types) of learning. Keywords Axon initial segment (AIS) Hippocampus GABA_A receptor clustering Learning impairment