1 / 10

Gap Junctions in the SCN

Gap Junctions in the SCN. YiDing Yu MCB 186 Circadian Biology. Autonomous Oscillators. Single-cell autonomous oscillators in the SCN (Welsh 1995) Synchronized firing in vivo Heterogeneity within the SCN rhythmicity (phase, period) neurotransmitter environmental response

zelia
Télécharger la présentation

Gap Junctions in the SCN

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Gap Junctions in the SCN YiDing Yu MCB 186 Circadian Biology

  2. Autonomous Oscillators • Single-cell autonomous oscillators in the SCN (Welsh 1995) • Synchronized firing in vivo • Heterogeneity within the SCN • rhythmicity (phase, period) • neurotransmitter • environmental response • rhythms controlled

  3. Multiple Phenotypes Rostral  Caudal (A  E) Moore et al. 2002

  4. How are single-cell oscillators synchronized in vivo? • Gap Junctions • Neurotransmitters • GABA • Vasoactive intestinal polypeptide (VIP) • Gastrin-releasing peptide (GRP) • Prokineticin 2 (PK2) • Maintain Rhythmicity? Aton et al. 2005

  5. Neuronal Gap Junctions • Spike-for-spike synchronization • Connexins expressed in the SCN • Connexin-36 found in murine and human neuronal gap junctions • Long et al. 2005 • Electrical coupling between 25% of neighboring cells • Electrical coupling lost in connexin-36 (Cx36) KO mice Soehl et al. 2005

  6. Hypothesis Are gap junctions necessary for maintaining rhythmicity among SCN cells? To what extent do gap junctions maintain synchrony between coupled cells? A. Gap junctions are not necessary to maintain rhythmicity of individual SCN cells B. Gap junctions are integral to maintaining synchrony between coupled cells

  7. Experiment 1: Rhythmicity in WT cells Electrode recording in various regions Dense vs. sparse neuronal population Dorsal shell vs. ventral core Neurotransmitter output (AVP, VIP, GRP) Experiment 2: Synchronization in WT cells Electrode recordings to find coupled SCN neurons Apply transmitter receptor antagonists to eliminate fast chemical synaptic transmission Protocol (in vitro) APPLY TREATMENT: Quinine (Cx36 specific) TREATMENT WASHOUT  Restore WT phenotype Positive control: Cx36 KO mice Negative control: Untreated WT mice

  8. Predicted Results • Experiment 1: Rhythmicity • No effect on individual cell rhythmicity upon treatment or washout, regardless of SCN region Long et al. 2005 • Experiment 2: Synchronization • Gap junction blocker treatment: Loss of synchrony between coupled cells; similar to Cx36 KO • Washout: Restore WT synchrony

  9. Implications & Further Studies • All cells remain rhythmic in experiment 1: Gap junctions do not function to maintain rhythmicity of oscillator cells • If some cells become arrhythmic: Gap junctions may play a role in the regulation of some SCN cells by other autonomous cell oscillators  Is this prevalent in a particular region of the SCN?

  10. Implications & Further Studies • Coupled WT cells lose synchrony upon treatment (experiment 2): Cx36 gap junctions are integral in maintaining coupling  Does coupling occur predominately in certain areas of the SCN? • If cells remain synchronized: Cx36 gap junctions are not necessary in maintaining coupling; Cx36 KO phenotype confounded • Possible other connexins involved? (Octanol, halothane) • Effects of gap junctions between neurons and glia? Glia and glia?

More Related