NPAS4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus

Hartzell, Andrea L.; Martyniuk, Kelly M.; Brigidi, G. Stefano; Heinz, Daniel A; Djaja, Nathalie A; Payne, Anja; Bloodgood, Brenda L.

doi:10.7554/elife.35927

Cited by 47 publications

(66 citation statements)

References 65 publications

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“…This observation is consistent with the Npas4 gene encoding two pools of mRNA that can be distinguished by the 5'UTR and subcellular localization within the PN. Furthermore, this interpretation suggests that exposure of mice to an EE, a stimulus that induces NPAS4 expression (Bloodgood et al, 2013;Hartzell et al, 2018); Figure 1L, M), should result in degradation of dendritic Npas4 mRNAs detected with all probe sets and a concomitant increase in somatic/nuclear mRNAs exclusively detected by CDS and 3'UTR probes. Indeed, following EE exposure dendritic Npas4 mRNAs in SR were depleted while nuclear/somatic mRNAs were significantly induced in SP ( Fig.…”

Section: Dendritically Localized Npas4 Mrna Encompasses a Long 5'utrmentioning

confidence: 96%

“…The amplitude of EPSPs was calculated using custom written software in Igor Pro (A.L.H. ; (Hartzell et al, 2018). Briefly, the baseline membrane potential was averaged from 0−98 ms before delivery of the stimulus pulse at 100 ms, and the peak amplitude between 2-20 ms poststimulus was quantified relative to baseline.…”

Section: Quantification and Statistical Analysismentioning

confidence: 99%

“…While the signals that result in NPAS4 induction have not been characterized, the downstream consequences of its expression are evident. NPAS4 functions to regulate neural circuit connectivity (Bloodgood et al, 2013;Hartzell et al, 2018;Spiegel et al, 2014;Weng et al, 2018), and Npas4 knockout mice exhibit severe cognitive deficits and seizures (Coutellier et al, 2012;Lin et al, 2008). Thus, understanding the type of activity that leads to NPAS4 expression will also illuminate what depolarizing signals are transformed by the genome into changes in circuit connectivity.…”

Section: Introductionmentioning

confidence: 99%

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WITHDRAWN: Genomic decoding of neuronal depolarization by stimulus-specific NPAS4 heterodimers

Brigidi

Hayes

Hartzell

et al. 2019

Preprint

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transport to the dendrites would result in inverted spatiotemporal dynamics from what we observed (Farris et al., 2014;Okuno et al., 2012).Summation of EPSPs during tetanic stimulation produces large NMDAR-mediated Ca signals and may, in principle, gate L-VGCCs localized to the apical dendrites or soma (Magee and Johnston, 1995;Marrion and Tavalin, 1998). To determine if one or both of these Ca sources are associated with synaptically-induced NPAS4, afferents in SR were stimulated in the presence of NMDAR or L-VGCC antagonists (CPP and Nim, respectively; Figure S1J).Blockade of NMDARs prevented NPAS4 induction in the dendrites and soma, whereas antagonism of L-VGCCs had no effect (Figure 1J). This result indicates that activation of NMDARs, but not L-VGCCs, accounts for both the dendritic and somatic NPAS4 protein induced by synaptic potentials. Thus, APs and EPSPs originating in SR engage distinct Ca sources to induce NPAS4 and result in NPAS4 expression patterns with unique spatiotemporal profiles along the somato-dendritic axis of the PN.NPAS4 protein has not been previously observed in the dendrites of PNs, thus we sought to determine if sensory experiences can induce dendritic NPAS4 in vivo. Mice (P21−28) were transferred from their home cage (HC) into an enriched environment (EE) for 5 minutes, and then returned to their HC (Figure 1K). At various time points after return to the HC (1−90 min), hippocampi were removed, fixed, sectioned and stained for NPAS4 and NeuN. In WT mice, NPAS4 protein was detected in SR 3−5 minutes after exposure to EE, followed by an increase in immunofluorescence in SP (Figure 1L, M), recapitulating our observations in acute slices.Deletion of Npas4 in excitatory neurons (Npas4 f/f :: Emx1 Cre ) eliminated the experiencedependent NPAS4 induction in SR and SP (Figure 1N), whereas Npas4 knockout in inhibitory neurons (Npas4 f/f :: GAD2 Cre ) had no impact (Figure 1O), indicating that dendritic and somatic NPAS4 protein is produced in PNs. Moreover, analysis of other hippocampal subregions revealed dendritically localized NPAS4 in CA3 PNs (Figure S2A−D) suggesting this expression profile may be a general feature of PNs. In dentate granule cells, NPAS4 protein was detected within minutes of return to the HC (Figure S2E−H) but was not clearly localized to dendrites, possibly due to their compact morphologies. Thus, immediately after novel sensory experiences NPAS4 protein is observed in the dendrites of PNs in vivo, reflecting increases in local synaptic transmission.

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Section: Dendritically Localized Npas4 Mrna Encompasses a Long 5'utrmentioning

confidence: 96%

Section: Quantification and Statistical Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

WITHDRAWN: Genomic decoding of neuronal depolarization by stimulus-specific NPAS4 heterodimers

Brigidi

Hayes

Hartzell

et al. 2019

Preprint

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“…Cb1r antibody has been generated against a synthetic peptide corresponding to AA 450 to 473 from rat Cb1r, recognized a band of approximately 48 kDa on Western blots of rat brain tissue lysate and has been tested on Cb1r knockout mice (manufacturer's datasheet). The Cb1r antibody stained a pattern of cellular morphology and distribution in the mouse cerebral cortex that is identical with previous reports (Hartzell et al, ).…”

Section: Methodssupporting

confidence: 90%

“…The Cb1r antibody stained a pattern of cellular morphology and distribution in the mouse cerebral cortex that is identical with previous reports (Hartzell et al, 2018).…”

Section: Antibody Characterizationsupporting

confidence: 89%

Dark exposure affects plasticity‐related molecules and interneurons throughout the visual system during adulthood

Carceller

Guirado

Nácher

2019

J of Comparative Neurology

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Several experimental manipulations, including visual deprivation, are able to induce critical period‐like plasticity in the visual cortex of adult animals. In this regard, many studies have analyzed the effects of dark exposure in adult animals, but still little is known about the role of interneurons and plasticity‐related molecules on such mechanisms. In this study, we analyzed the effects of 10 days of dark exposure on the connectivity and structure of interneurons, both in the primary visual cortex and in the rest of cerebral regions implicated in the transmission of visual stimulus. We found that this environmental manipulation induces changes in the expression of synaptic molecules throughout the visual pathway and in the structure of interneurons in the primary visual cortex. Moreover, we found altered expression in the polysialylated form of the neural cell adhesion molecule and in perineuronal nets surrounding parvalbumin expressing interneurons, suggesting that these plasticity‐related molecules may be involved in the changes produced by dark exposure. Together, our findings indicate that dark exposure produces an important alteration of inhibitory circuits and molecules related to their plasticity, not only in the visual cortex but throughout the visual pathway.

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Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease

Asim,

Wang,

Waris

et al. 2024

BioFactors

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Cholecystokinin (CCK) plays a key role in various brain functions, including both health and disease states. Despite the extensive research conducted on CCK, there remain several important questions regarding its specific role in the brain. As a result, the existing body of literature on the subject is complex and sometimes conflicting. The primary objective of this review article is to provide a comprehensive overview of recent advancements in understanding the central nervous system role of CCK, with a specific emphasis on elucidating CCK's mechanisms for neuroplasticity, exploring its interactions with other neurotransmitters, and discussing its significant involvement in neurological disorders. Studies demonstrate that CCK mediates both inhibitory long‐term potentiation (iLTP) and excitatory long‐term potentiation (eLTP) in the brain. Activation of the GPR173 receptor could facilitate iLTP, while the Cholecystokinin B receptor (CCKBR) facilitates eLTP. CCK receptors' expression on different neurons regulates activity, neurotransmitter release, and plasticity, emphasizing CCK's role in modulating brain function. Furthermore, CCK plays a pivotal role in modulating emotional states, Alzheimer's disease, addiction, schizophrenia, and epileptic conditions. Targeting CCK cell types and circuits holds promise as a therapeutic strategy for alleviating these brain disorders.

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NPAS4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus

Cited by 47 publications

References 65 publications

WITHDRAWN: Genomic decoding of neuronal depolarization by stimulus-specific NPAS4 heterodimers

WITHDRAWN: Genomic decoding of neuronal depolarization by stimulus-specific NPAS4 heterodimers

Dark exposure affects plasticity‐related molecules and interneurons throughout the visual system during adulthood

Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease

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