Homeostatic synaptic scaling establishes the specificity of an associative memory

Wu, Chi-Hong; Ramos, Raul; Katz, Donald B.; Turrigiano, Gina G.

doi:10.1016/j.cub.2021.03.024

Cited by 44 publications

(75 citation statements)

References 61 publications

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“…This result, which supports the second alternative above, might corresponds to cellular and network-level homeostatic plasticity mechanisms that aim to rebalance the early potentiated activity following the early acquisition phase (Maffei and Fontanini, 2009;Turrigiano, 2011;Keck et al, 2017). Interestingly, it was recently shown that synaptic scaling, a form of homeostatic plasticity, occurs at the same epoch and is essential for the transition from general to specific CTA (Wu et al, 2021). Comparing the relation between the number of neurons that increased or decreased their activity over the post-CTA hours further supported this hypothesis: while in the Fam group increases and decreases were anticorrelated (suggesting a drift effect), in the Exp group they were correlated (Fig.…”

Section: Discussionsupporting

confidence: 74%

Distinct progressions of neuronal activity changes underlie the formation and consolidation of a gustatory associative memory

Arieli

Younis

Moran

2021

Preprint

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Acquiring new memories is a multi-stage process. Ample of studies have convincingly demonstrated that initially acquired memories are labile, and only stabilized by later consolidation processes. These multiple phases of memory formation are known to involve modification of both cellular excitability and synaptic connectivity, which in turn change neuronal activity at both the single neuron and ensemble levels. However, the specific mapping between the known phases of memory and the observed changes in neuronal activity remains unknown. Here we address this unknown in the context of conditioned taste aversion learning by continuously tracking gustatory cortex (GC) neuronal taste responses from alert rats in the 24 hours following a taste-malaise pairing. We found that the progression of neuronal activity changes in the GC depend on the neuronal organizational level. The population response changed continuously; these changes, however, were only reflected in the population mean amplitude during the acquisition and consolidation phases, and in the known quickening of the ensemble state dynamics after the time of consolidation. Together our results demonstrate how complex dynamics in different representational level of cortical activity underlie the formation and stabilization of memory within the cortex.

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Section: Discussionsupporting

confidence: 74%

Distinct progressions of neuronal activity changes underlie the formation and consolidation of a gustatory associative memory

Arieli

Younis

Moran

2021

Preprint

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“…Slice recordings were obtained between P24-P29, well within the classical visual system CP (Espinosa and Stryker, 2012). We compared two methods of CNO delivery: intraperitoneal injections (IP, 5 mg/kg, every 12 hours) as described previously (Wu et al, 2021), and by inclusion of CNO in the drinking water (DW, 0.05 mg/mL, ad libitum ). Under both delivery methods, the average mEPSC amplitude of hM4Di-positive L2/3 pyramidal neurons (DR + CNO) increased significantly relative to hM4Di-negative neurons from the uninfected hemisphere (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Chronic chemogenetic activity suppression induces synaptic scaling in L2/3 pyramidal neurons during the CP In order to study the developmental regulation of homeostatic plasticity mechanisms, we needed a paradigm that would allow us to induce comparable activity-deprivation at different developmental stages. DREADD-mediated inhibition in vivo has been shown to induce synaptic scaling up in insular cortex (Wu et al, 2021), so we adapted this approach for use in L2/3 pyramidal neurons in V1, where we know that homeostatic and intrinsic plasticity are co-induced by visual deprivation during the classic visual system CP (Lambo and Turrigiano, 2013).…”

Section: Resultsmentioning

confidence: 99%

Developmental Regulation of Homeostatic Plasticity in Mouse Primary Visual Cortex

Wen

Turrigiano

2021

Preprint

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Homeostatic plasticity maintains network stability by adjusting excitation, inhibition, or the intrinsic excitability of neurons, but the developmental regulation and coordination of these distinct forms of homeostatic plasticity remains poorly understood. A major contributor to this information gap is the lack of a uniform paradigm for chronically manipulating activity at different developmental stages. To overcome this limitation, we utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to directly suppress neuronal activity in layer (L) 2/3 of mouse primary visual cortex (V1) at two important developmental timepoints: the classic visual system critical period (CP, P24-29), and adulthood (P45-55). We show that 24 hours of DREADD-mediated activity suppression simultaneously induces excitatory synaptic scaling up and intrinsic homeostatic plasticity in L2/3 pyramidal neurons during the CP, consistent with previous observations using prolonged visual deprivation. Importantly, manipulations known to block these forms of homeostatic plasticity when induced pharmacologically or via visual deprivation also prevented DREADD-induced homeostatic plasticity. We next used the same paradigm to suppress activity in adult animals. Surprisingly, while excitatory synaptic scaling persisted into adulthood, intrinsic homeostatic plasticity was completely absent. Finally, we found that homeostatic changes in quantal inhibitory input onto L2/3 pyramidal neurons were absent during the CP but present in adults. Thus, the same population of neurons can express distinct sets of homeostatic plasticity mechanisms at different development stages. Our findings suggest that homeostatic forms of plasticity can be recruited in a modular manner according to the evolving needs of a developing neural circuit.

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“…Brain slices were produced following our previously documented protocols (Miska et al, 2018;Cary & Turrigiano, 2021;Wu, Ramos, et al, 2021). Briefly, rats (p28-p34) were anesthetized with isoflurane, decapitated, and the brain was swiftly dissected out into ice cold carbogenated (95% O2, 5% CO2) standard ACSF (in mM: 126NaCl, 25 NaHCO3, 3 KCl, 2 CaCl2, 2 MgSO4, 1 NaH2PO4, 0.5 Na-Ascorbate, osmolarity adjusted to 310-315 mOsm with dextrose, pH 7.35).…”

Section: Ex-vivo Acute Brain-slice Preparationmentioning

confidence: 99%

“…Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion concentration of LiCl) produced a generali ed aversion that as still present at the 24 hours time point (Wu, Ramos, et al, 2021). Here, we explored this more persistent generalized aversion to determine how long it lasts, and the cellular basis of its persistence.…”

Section: Introductionmentioning

confidence: 99%

Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion

Ramos

Turrigiano

2022

Preprint

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Generalization is an adaptive mnemonic process in which an animal can leverage past learning experiences to navigate future scenarios, but overgeneralization is a hallmark feature of anxiety disorders. Therefore, understanding the synaptic plasticity mechanisms that govern memory generalization and its persistence is an important goal. Here, we demonstrate that strong CTA conditioning results in a long-lasting generalized aversion that persists for at least two weeks. Using brain slice electrophysiology and activity-dependent labeling of the conditioning-active neuronal ensemble within the gustatory cortex, we find that strong CTA conditioning induces a long-lasting increase in synaptic strengths that occurs uniformly across superficial and deep layers of GC. Repeated exposure to salt, the generalized tastant, causes a rapid attenuation of the generalized aversion that correlates with a reversal of the CTA-induced increases in synaptic strength. Unlike the uniform strengthening that happens across layers, reversal of the generalized aversion results in a more pronounced depression of synaptic strengths in superficial layers. Finally, the generalized aversion and its reversal do not impact the acquisition and maintenance of the aversion to the conditioned tastant (saccharin). The strong correlation between the generalized aversion and synaptic strengthening, and the reversal of both in superficial layers by repeated salt exposure, strongly suggests that the synaptic changes in superficial layers contribute to the formation and reversal of the generalized aversion. In contrast, the persistence of synaptic strengthening in deep layers correlates with the persistence of CTA. Taken together, our data suggest that layer-specific synaptic plasticity mechanisms separately govern the persistence and generalization of CTA memory.

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Homeostatic synaptic scaling establishes the specificity of an associative memory

Cited by 44 publications

References 61 publications

Distinct progressions of neuronal activity changes underlie the formation and consolidation of a gustatory associative memory

Distinct progressions of neuronal activity changes underlie the formation and consolidation of a gustatory associative memory

Developmental Regulation of Homeostatic Plasticity in Mouse Primary Visual Cortex

Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion

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