Dynamics of dendritic spines in the mouse auditory cortex during memory formation and memory recall |
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Authors: | Kaja Ewa Moczulska Juliane Tinter-Thiede Manuel Peter Lyubov Ushakova Tanja Wernle Brice Bathellier Simon Rumpel |
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Affiliation: | Research Institute of Molecular Pathology, 1030 Vienna, Austria |
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Abstract: | Long-lasting changes in synaptic connections induced by relevant experiences are believed to represent the physical correlate of memories. Here, we combined chronic in vivo two-photon imaging of dendritic spines with auditory-cued classical conditioning to test if the formation of a fear memory is associated with structural changes of synapses in the mouse auditory cortex. We find that paired conditioning and unpaired conditioning induce a transient increase in spine formation or spine elimination, respectively. A fraction of spines formed during paired conditioning persists and leaves a long-lasting trace in the network. Memory recall triggered by the reexposure of mice to the sound cue did not lead to changes in spine dynamics. Our findings provide a synaptic mechanism for plasticity in sound responses of auditory cortex neurons induced by auditory-cued fear conditioning; they also show that retrieval of an auditory fear memory does not lead to a recapitulation of structural plasticity in the auditory cortex as observed during initial memory consolidation.Mammalian brains are characterized by a tremendous level of plasticity. This plasticity is believed to underlie the ability to extract and store information about past experiences and is crucial for animals and humans to interact adaptively in a changing environment. Therefore, detection and localization of a physical representation of a memory has been an intriguing aspect for a long time (1). Plastic changes in synapses are believed to be substrates of memory (2). The development of imaging techniques that allow chronic monitoring of dendritic spines, the morphological correlates of excitatory synapses on pyramidal neurons, in the living animal has provided valuable insights in the dynamics of neuronal circuits (3–5). It has recently been shown that not only chronic perturbations of sensory inputs (6, 7), but also temporally restricted learning experiences, impact the turnover of synaptic structures in the motor cortex and frontal association cortex of the mouse (8–10) and the high vocal center in zebra finches (11).Auditory-cued fear conditioning (ACFC) is an associative learning paradigm that has been widely used to analyze mechanisms of learning in the auditory modality (12). During a conditioning session, subjects quickly learn to associate a previously neutral sound cue [the conditional stimulus (CS)] with an aversive stimulus like a mild foot shock [unconditional stimulus (US)]. It is well established that memory traces after initial formation undergo several processes at different time scales that lead to their consolidation and render them to a stable state that is, e.g., resistant to trauma introduced by an electroconvulsive shock (13). Interestingly, similar molecular cascades are triggered not only during memory formation, but also when a memory trace is retrieved (14, 15). Furthermore, memory traces that were recently retrieved become sensitive again to manipulations like electroconvulsive shock (16), blockade of NMDA receptors (17), or blockade of protein synthesis (18). These similarities have been suggested to reflect remodeling of memory traces following recall (14, 19). However, data on the dynamics of synaptic structures during memory recall is lacking up to date.A number of brain structures have been identified mediating the formation of a memory induced by ACFC (12). Whereas inputs via the auditory cortex (ACx) to the amygdala, an essential brain structure for this learning paradigm, appear to be always sufficient to support fear conditioning (20), their necessity can depend on the spectrotemporal properties of the auditory CS (21, 22). The ACx as the primary sensory cortical area for the auditory modality has been extensively analyzed in the past during classical conditioning to sound stimuli (23–25) or pairing of sounds with artificial stimulation of the cholinergic system, which can substitute for aspects of the US (26–28). These paradigms lead to changes in the receptive fields of ACx neurons that are specific to the conditioned sound. There is evidence based on local pharmacological or optogenetic manipulations that plasticity of the ACx itself is necessary for experience-induced alterations in sound responses and does not simply reflect plasticity elsewhere in the auditory pathway (29, 30). Indeed, there is evidence based on electrophysiological recordings that synaptic plasticity at intracortical synapses can be induced by pairing of a sound with stimulation of the cholinergic system in vivo (28). Structural plasticity following ACFC has been observed in the frontal association cortex (10). However, it remains elusive if plasticity in sound responses in the ACx induced by ACFC (23–25) also has a structural correlate at the synaptic level.In this study, we asked two major questions: Does ACFC in behaving mice induce structural plasticity in synaptic circuits of the ACx? To what extent do memory formation and memory recall share similarities at the level of synaptic structures? We addressed these questions by combining sound-cued fear conditioning and memory testing with chronic in vivo imaging of dendritic spines in the ACx. |
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Keywords: | learning auditory fear conditioning reconsolidation |
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