Synaptic activation of T-type Ca2+ channels via mGluR activation in the primary dendrite of mitral cells.
Mitral cells are the primary output of the olfactory bulb, projecting to many higher brain areas. Understanding how mitral cells process and transmit information is key to understanding olfactory perception. Mitral dendrites possess high densities of voltage-gated channels, are able to initiate and propagate orthodromic and antidromic action potentials, and release neurotransmitter. We show that mitral cells also possess a low-voltage-activated T-type Ca(2+) current. Immunohistochemistry shows strong Cav3.3 labeling in the primary dendrite and apical tuft with weaker staining in basal dendrites and no staining in somata. A low-voltage-activated Ca(2+) current activates from -68 mV, is blocked by 500 microM Ni(2+) and 50 microM NNC 55-0396, but is insensitive to 50 microM Ni(2+) and 500 microM isradipine. 2-photon Ca(2+) imaging shows that T channels are functionally expressed in the primary dendrite where their activity determines the resting [Ca(2+)] and are responsible for subthreshold voltage-dependent Ca(2+) changes previously observed in vivo. Application of the group 1 mGluR agonist dihydroxyphenylglycine (DHPG) (50 microM) robustly upregulates T-channel current in the primary and apical tuft dendrite. Olfactory nerve stimulation generates a long-lasting depolarization, and we show that mGluRs recruit T channels to contribute approximately 36% of the voltage integral of this depolarization. The long-lasting depolarization results in sustained firing and block of T channels decreased action potential firing by 84.1 +/- 4.6%. Therefore upregulation of T channels by mGluRs is required for prolonged firing in response to olfactory nerve input.
Johnston
Jamie
J
Department of Biology, University of Victoria, Victoria, British Columbia, Canada.
Delaney
Kerry R
KR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology*; D009832:Olfactory Nerve / Q000502:physiology; D018408:Patch-Clamp Techniques; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
C498197:Cacna1g protein, mouse; C534770:Cacna1i protein, mouse; D020747:Calcium Channels, T-Type; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D002118:Calcium