The localization and physiological effects of cannabinoid receptor 1 in the brain stem auditory system of the chick

摘要: Acoustic stimuli drive high rates of neural activity and these can be relatively long-lasting. In vivo spontaneous firing average 100Hz even lacking auditory (Warchol Dallos, 1990). Neurons must able to respond in a consistent manner throughout the entirety stimulus code this information effectively. Additionally, encoding important about acoustic is not simply duration as it requires that action potentials precisely timed with respect stimulus. brain stem system possess number features optimize their ability maintain sustained responses. Important adaptations rigorous demands coding have been identified cochlear nucleus chick, magnocellularis (NM). This area key for processing time-locked signals from nerve (cnVIII) relaying laminaris (NL), where analyses interaural time differences assist tasks such localization sound source (Sullivan Konishi, 1984, Takahashi et al., Carr 1990, Warchol Overholt 1992). One adaptation towards accomplishing NM's role accurately seen nature its innervation. NM neurons receive large excitatory calyceal input only 2-3 cnVIII fibers (Carr Boudreau, 1991). Each afferents capable producing suprathreshold currents through release glutamate, resulting neurotransmission safety factor (Parks Rubel, 1978, Hackett 1982, Zhang Trussell, 1994b, a). produce single, strong post-synaptic potential (EPSP) mediated primarily via AMPA receptor activation. Little jitter or temporal summation observed which aided by low-threshold K+ channels help ensure minimal refractory period (Reyes 1994, 1994b). While synaptic allow fire at very rates, depression become serious impediment ongoing stimuli. short-term effect progressive decline size postsynaptic responses same desensitization appears major limitation (Trussell 1993, Otis 1996), but vesicle depletion presents second (AP) (Brenowitz 2001). addition, glutamatatergic autoreceptor activation may contribute phenomenon (Barnes-Davies Forsythe, 1995, von Gersdorff 1997). Failing limit would detrimental prevent stimulus. Strong both (Hackett 1994a) NL (Kuba 2002, Cook 2003) slice preparations. It possible procedure itself, i.e. extraction slice, removes endogenous necessary attenuate depression. For example, descending GABAergic inhibition superior olivary (SON) play dual role, working pre- post-synaptically cnVIII-NM synapse preserve 1989, Code Lachica 1994). GABAA receptors influence excitability, tightening window postsynaptically (Hyson Monsivais 2000) while GABAB conserve glutamate during 1998). doing so, reduces across train stimuli, limiting decrease response. Another mechanism regulating glutamatergic signaling cannabinoid (CB) signaling, has already shown modulatory other sensory systems (Straiker 1999a, Straiker 1999b, Czesnik 2007, Deshmukh Thornton-Jones Nyilas 2009). Our laboratory recently reported distribution 1 (CB1) mRNA chick (Stincic Hyson, 2008). While little expression was found NL, ganglion (vestibular portion) displayed robust CB1 expression. finding suggested (CG) well. expressed dorsal rats (Mailleux Vanderhaeghen, 1992) CBs modulate plasticity nuclei (Penzo Pena, 2009, Zhao CB retroinhibition also medial trapezoid body (MNTB) (Kushmerick 2004). significant because MNTB an receives input. Taken together, previous reports suggest likely well. CB acts metabotropic share some traits classical neurotransmitter systems, differs aspects. When activated, trigger 2nd messenger cascades Gi/o-proteins (Howlett Fleming, Howlett, 1985, Howlett 1986). Vesicles, however, are required transport since (eCBs) lipophillic crossing cell membrane either unaided facilitated diffusion (Beltramo 1997, Hillard Once released into cells, eCBs activate located on presynaptic cell. Functional localized presynaptically axonal terminals almost no exceptions adult animals (Schlicker Kathmann, 2001). A voltage-gated Ca2+ (N-type P/Q-type) (Caulfield Brown, 1992, Felder Mackie 1993), leading reduction vesicles upon arrival terminal. way, reduce amount cleft, subsequently lessening factors depression. If additional optimizing synapse, present effective modulating transmission. study first establishes presence using situ hybridization (ISH) immunohistochemistry (IHC), then documents