Mapping homeostatic synaptic plasticity using cable properties of dendrites

Queenan, Bridget N.; Lee, Kea Joo; Tan, Han L.; Huganir, Richard L.; Vicini, Stefano; Pak, Daniel T.S.

doi:10.1016/j.neuroscience.2015.12.017

Cited by 4 publications

(4 citation statements)

References 20 publications

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“…Consistent with prior studies, 16,30 we found that homeostatic compensations of excitatory hippocampal neurons following sustained inactivity (induced via application of the sodium channel antagonist TTX) occurred only at excitatory post-synapses of CA3 neurons (Fig. 1B,E); in contrast, DG (Fig.…”

Section: Resultssupporting

confidence: 92%

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Kappa opioid receptors regulate hippocampal synaptic homeostasis and epileptogenesis

et al. 2017

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SummaryObjective: Homeostatic synaptic plasticity (HSP) serves as a gain control mechanism at central nervous system (CNS) synapses, including those between the dentate gyrus (DG) and CA3. Improper circuit control of DG-CA3 synapses is hypothesized to underlie epileptogenesis. Here, we sought to (1) identify compounds that preferentially modulate DG-CA3 synapses in primary neuronal culture and (2) determine if these compounds would delay or prevent epileptogenesis in vivo. Methods: We previously developed and validated an in vitro assay to visualize the behavior of DG-CA3 synapses and predict functional changes. We used this "synapse-on-chip" assay (quantification of synapse size, number, and type using immunocytochemical markers) to dissect the mechanisms of HSP at DG-CA3 synapses. Using chemogenetic constructs and pharmacological agents we determined the signaling cascades necessary for gain control at DG-CA3 synapses. Finally, we tested the implicated cascades (using kappa opioid receptor (OR) agonists and antagonists) in two models of epileptogenesis: electrical amygdala kindling in the mouse and chemical (pentylenetetrazole) kindling in the rat. Results: In vitro, synapses between DG mossy fibers (MFs) and CA3 neurons are the primary homeostatic responders during sustained periods of activity change. Kappa OR signaling is both necessary and sufficient for the homeostatic elaboration of DG-CA3 synapses, induced by presynaptic DG activity levels. Blocking kappa OR signaling in vivo attenuates the development of seizures in both mouse and rat models of epilepsy.

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Section: Resultssupporting

confidence: 92%

“…3A–C, Fig. S4), supporting previous findings that homeostatic synaptic compensations in vitro occurs preferentially at proximal DG-CA3 synapses 16,30 .…”

Section: Resultssupporting

confidence: 90%

Kappa opioid receptors regulate hippocampal synaptic homeostasis and epileptogenesis

et al. 2017

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“…Ten recordings per cell with the stimulus administration were made, and the average ratio of the second pulse to the first pulse was calculated for both groups. Recordings of mEPSC were performed on cells during voltage clamp (at −70 mV), while 1 µM TTX and 25 µM BMR were administered via y-tube to block sodium channels and GABA-mediated inhibitory currents (respectively) 100 , 101 . For mEPSC amplitude and frequency analyses, templates were made of stereotypical mEPSC events from a subset of cells in each group using the Clampfit 10.7 software (Molecular Devices LLC, Sunnyvale, CA).…”

Section: Methodsmentioning

confidence: 99%

High-frequency head impact causes chronic synaptic adaptation and long-term cognitive impairment in mice

et al. 2021

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Repeated head impact exposure can cause memory and behavioral impairments. Here, we report that exposure to non-damaging, but high frequency, head impacts can alter brain function in mice through synaptic adaptation. High frequency head impact mice develop chronic cognitive impairments in the absence of traditional brain trauma pathology, and transcriptomic profiling of mouse and human chronic traumatic encephalopathy brain reveal that synapses are strongly affected by head impact. Electrophysiological analysis shows that high frequency head impacts cause chronic modification of the AMPA/NMDA ratio in neurons that underlie the changes to cognition. To demonstrate that synaptic adaptation is caused by head impact-induced glutamate release, we pretreated mice with memantine prior to head impact. Memantine prevents the development of the key transcriptomic and electrophysiological signatures of high frequency head impact, and averts cognitive dysfunction. These data reveal synapses as a target of high frequency head impact in human and mouse brain, and that this physiological adaptation in response to head impact is sufficient to induce chronic cognitive impairment in mice.

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“…Increased dendritic complexity can also lead to an increase of IPSC and mEPSC frequency because it allows for increased synaptic connectivity 37 , 38 . Whole-cell recordings with a potassium chloride-based internal solution can accurately detect currents originating in dendrites up to 100 μm from the soma 39 . The increased dendritic complexity seen in D1 SPNs of the MMP-1OE mice occurred between 60 μm and 80 μm from the soma, thus, the increased synaptic transmission observed may be due in part to the altered dendritic tree.…”

Section: Discussionmentioning

confidence: 99%

MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core

Al-Muhtasib

Forcelli

Conant

et al. 2018

Sci Rep

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Protease activated receptor-1 (PAR-1) and its ligand, matrix metalloproteinase-1 (MMP-1), are altered in several neurodegenerative diseases. PAR-1/MMP-1 signaling impacts neuronal activity in various brain regions, but their role in regulating synaptic physiology in the ventral striatum, which is implicated in motor function, is unknown. The ventral striatum contains two populations of GABAergic spiny projection neurons, D1 and D2 SPNs, which differ with respect to both synaptic inputs and projection targets. To evaluate the role of MMP-1/PAR-1 signaling in the regulation of ventral striatal synaptic function, we performed whole-cell recordings (WCR) from D1 and D2 SPNs in control mice, mice that overexpress MMP-1 (MMP-1OE), and MMP-1OE mice lacking PAR-1 (MMP-1OE/PAR-1KO). WCRs from MMP1-OE mice revealed an increase in spontaneous inhibitory post-synaptic current (sIPSC), miniature IPSC, and miniature excitatory PSC frequency in D1 SPNs but not D2 SPNs. This alteration may be partially PAR-1 dependent, as it was not present in MMP-1OE/PAR-1KO mice. Morphological reconstruction of D1 SPNs revealed increased dendritic complexity in the MMP-1OE, but not MMP-1OE/PAR-1KO mice. Moreover, MMP-1OE mice exhibited blunted locomotor responses to amphetamine, a phenotype also observed in MMP-1OE/PAR-1KO mice. Our data suggest PAR-1 dependent and independent MMP-1 signaling may lead to alterations in striatal neuronal function.

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Mapping homeostatic synaptic plasticity using cable properties of dendrites

Cited by 4 publications

References 20 publications

Kappa opioid receptors regulate hippocampal synaptic homeostasis and epileptogenesis

Kappa opioid receptors regulate hippocampal synaptic homeostasis and epileptogenesis

High-frequency head impact causes chronic synaptic adaptation and long-term cognitive impairment in mice

MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core

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