A common human brain-derived neurotrophic factor polymorphism leads to sustained depression of excitatory synaptic transmission by isoflurane in hippocampus
Williams, R. A.; Johnson, K. W.; Lee, F. S.; Hemmings, H. C.; Platholi, J.
Show abstract
Multiple presynaptic and postsynaptic targets have been identified for the reversible neurophysiological effects of general anesthetics on synaptic transmission and neuronal excitability. However, the synaptic mechanisms involved in persistent depression of synaptic transmission resulting in more prolonged neurological dysfunction following anesthesia are less clear. Here, we show that brain-derived neurotrophic factor (BDNF), a growth factor implicated in synaptic plasticity and dysfunction, enhances glutamate synaptic vesicle exocytosis, and that attenuation of vesicular BDNF release by isoflurane contributes to transient depression of excitatory synaptic transmission in mice. This reduction in synaptic vesicle exocytosis was irreversible in neurons that release less endogenous BDNF due to a polymorphism (BDNF Val66Met) compared to wild-type mouse hippocampal neurons following isoflurane exposure. These effects were prevented by exogenous application of BDNF. Our findings identify a role for a common human BDNF single nucleotide polymorphism (Val66Met; rs6265) in persistent changes of synaptic function following isoflurane exposure. These persistent alterations in excitatory synaptic transmission have important implications for the role of genotype in anesthetic effects on synaptic plasticity and neurocognitive function.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Inhibition of noradrenaline-dependent synaptic transmission in the dorsal raphe nucleus by alpha2-adrenergic receptors 96%
- Rapid Hippocampal Synaptic Potentiation Induced By Ketamine Metabolite (2R,6R)-Hydroxynorketamine Persistently Primes Synaptic Plasticity 94%
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses 94%
Similar papers in this journal
- Chondroitinase and antidepressants promote plasticity by releasing TRKB from dephosphorylating control of PTPσ in parvalbumin neurons 94%
- Modulation of hippocampal network oscillation by PICK1-dependent cell surface expression of mGlu3 receptors 94%
- Alterations of adult prefrontal circuits induced by early postnatal fluoxetine treatment mediated by 5-HT7 receptors. 93%
Similar papers in this journal
- State-dependent GABAergic regulation of striatal spiny projection neuron excitability 94%
- Adult medial habenula neurons require GDNF receptor GFRalpha1 for synaptic stability and function 92%
- Astroglial dysfunctions drive aberrant synaptogenesis in developing brain with lengthy general anesthesia 91%
Similar papers in this journal
- Regulation of dopamine release by tonic activity patterns in the striatal brain slice 91%
- Shared and distinct brain regions targeted for immediate early gene expression by ketamine and psilocybin 91%
- Kappa opioid receptor induces epigenetic silencing of brain derived neurotropic factor via HDAC5 in treatment-resistant depression 91%
Similar papers in this journal
- Hsp47 Promotes Biogenesis of Multi-subunit Neuroreceptors in the Endoplasmic Reticulum 94%
- The cation channel mechanisms of subthreshold inward depolarizing currents in the VTA dopaminergic neurons and their roles in the chronic-stress-induced depression-like behavior 93%
- All-trans retinoic acid induces synaptopodin-dependent metaplasticity in mouse dentate granule cells 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.