Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin

Abstract

Deletion of the autism candidate molecule neurobeachin (Nbea), a large PH-BEACH-domain containing neuronal protein, has been shown to affect synaptic function by interfering with neurotransmitter receptor targeting and dendritic spine formation. Previous analysis of mice lacking one allele of the Nbea gene identified impaired spatial learning and memory in addition to altered autism-related behaviours. However, no functional data from living heterozygous Nbea mice (Nbea+/−) are available to corroborate the behavioural phenotype. Here, we explored the consequences of Nbea haploinsufficiency on excitation/inhibition balance and synaptic plasticity in the intact hippocampal dentate gyrus of Nbea+/− animals in vivo by electrophysiological recordings. Based on field potential recordings, we show that Nbea+/− mice display enhanced LTP of the granule cell population spike, but no differences in basal synaptic transmission, synapse numbers, short-term plasticity, or network inhibition. These data indicate that Nbea haploinsufficiency causes remarkably specific alterations to granule cell excitability in vivo, which may contribute to the behavioural abnormalities in Nbea+/− mice and to related symptoms in patients.

Latent toxoplasmosis impairs learning and memory yet strengthens short-term and long-term hippocampal synaptic plasticity at perforant pathway-dentate gyrus, and Schaffer collatterals-CA1 synapses

“…Therefore, it can be deduced that manipulation of synaptic proteins by T. gondii might underlie the learning deficit along with LTP augmentation in the infected rats. Similar to our finding, the coincidence of potentiated LTP and impaired spatial learning and memory has been reported in the autism candidate molecule, neurobeachin (Nbea) haploinsufficient (Nbea + /−) mice 63 . Meanwhile, it has been shown that constitutive activation of cAMP-responsive element-binding protein (CREB) in mice is associated with enhanced LTP and learning deficit in spatial task 64 .…”

“…Meanwhile, it has been shown that constitutive activation of cAMP-responsive element-binding protein (CREB) in mice is associated with enhanced LTP and learning deficit in spatial task 64 . Interestingly, Nbea + / − mice developed enhanced LTP with increased phosphorylated CREB level in CA1 and DG, despite decreased spatial learning ability 63 . It is proposed that bi-directional and dynamic synaptic plasticity is critical to enhance storage capacity and optimize memory storage to decline memory errors.…”

All-trans retinoic acid induces synaptopodin-dependent metaplasticity in mouse dentate granule cells

“…After stable anesthesia was reached, atRA (10 mg/kg in 5% DMSO) or vehicle-only was intraperitoneally injected (blind to experimenter). The surgery and electrode placement were performed as previously described ( Jedlicka et al, 2011 ; Muellerleile et al, 2020 ). Briefly, the mouse was placed in a stereotactic frame (David Kopf Instruments) and local anesthesia with prilocaine (Xylonest 1%, Astra Zeneca, s.c. to the scalp) was applied.…”

NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease

“…However, an increase or decrease in the expression of AMPA receptors alone cannot explain the entire complex of pathological changes in neurons, which occurs in NLRP3 knockout mice and under the Aβ action. Thus, the increase in the fEPSP amplitude directly indicates the strength of excitatory synaptic transmission, i.e., how quickly the presynapse releases the neurotransmitter and binds to the ligand-dependent channel [ 54 ]. According to our data, this is the most sensitive indicator of impaired synaptic transmission in NLRP3 knockout mice.…”