Abstract
In both invertebrate and vertebrate models of synaptic plasticity, signaling via the putative “retrograde messenger” nitric oxide (NO) has been hypothesized to serve as a critical link between functional and structural alterations at pre- and postsynaptic sites. However, while in vitro models of synaptic plasticity have consistently implicated NO signaling in linking postsynaptic induction mechanisms with accompanying presynaptic changes, a convincing role of such “retrograde signaling” in mammalian memory formation has remained elusive. Using auditory Pavlovian fear conditioning, we show that synaptic plasticity and NO signaling in the lateral nucleus of the amygdala (LA) regulate the expression of the ERK-driven immediate early gene early growth response gene I (EGR-1) in regions of the auditory thalamus that are presynaptic to the LA. Further, antisense knockdown of EGR-1 in the auditory thalamus impairs both fear memory consolidation and the training-induced elevation of two presynaptically localized proteins in the LA. These findings indicate that synaptic plasticity and NO signaling in the LA during auditory fear conditioning promote alterations in ERK-driven gene expression in auditory thalamic neurons that are required for both fear memory consolidation as well as presynaptic correlates of fear memory formation in the LA, and provide general support for a role of NO as a “retrograde signal” in mammalian memory formation.
Highlights
In vertebrate models of synaptic plasticity, it is widely accepted that N-methyl-D-aspartate receptor (NMDAR)-driven recruitment of intracellular signaling pathways promotes long-term plastic change and memory through alterations of transcription and translation and accompanying morphological changes at both pre- and postsynaptic sites
Our findings support the hypothesis that NMDAR-driven synaptic plasticity and nitric oxide (NO) signaling in the LA drive changes in gene expression in thalamic projection neurons that are critical for fear memory formation by promoting presynaptic aspects of plasticity at LA synapses, and support a more general role for NO-driven “retrograde signaling” in mammalian memory formation
Together with our recent observations that NO signaling in the LA is required for fear memory consolidation (Schafe et al, 2005; Ota et al, 2008), we have hypothesized that synaptic plasticity and NO signaling in the LA drive changes in ERK-driven gene expression in MGm/PIN projection neurons that contribute to presynaptic aspects of plasticity in the LA and to fear memory formation
Summary
In vertebrate models of synaptic plasticity, it is widely accepted that N-methyl-D-aspartate receptor (NMDAR)-driven recruitment of intracellular signaling pathways promotes long-term plastic change and memory through alterations of transcription and translation and accompanying morphological changes at both pre- and postsynaptic sites. While in vitro studies have convincingly supported a role for NO as a “retrograde messenger” in hippocampal synaptic plasticity (Arancio et al, 1996a,b), a corresponding role in hippocampal memory formation has remained elusive and controversial This is likely due, in part, to the relative complexity of hippocampal-dependent learning tasks, which can make identification of the relevant synapses underlying acquisition of the task problematic. We show that NMDAR-driven synaptic plasticity and NO signaling in the LA regulate ERK-driven gene expression in MGm/PIN projection neurons that contributes to both fear memory consolidation and to alterations in presynaptically localized proteins at LA synapses. Our findings support the hypothesis that NMDAR-driven synaptic plasticity and NO signaling in the LA drive changes in gene expression in thalamic projection neurons that are critical for fear memory formation by promoting presynaptic aspects of plasticity at LA synapses, and support a more general role for NO-driven “retrograde signaling” in mammalian memory formation. “Paired” rats received three conditioning trials consisting of a 20 s, 5 kHz, 75 dB tone that co-terminated with a 1 s, 0.5-mA
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
