Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation

Abstract

Background: The formation of long-term memory (LTM) and the late phase of long-term potentiation (L-LTP) depend on macromolecule synthesis, translation, and transcription in neurons. vesl-1S (VASP/Ena-related gene upregulated during seizure and LTP, also known as homer-1a) is an LTP-induced immediate early gene. The short form of Vesl (Vesl-1S) is an alternatively spliced isoform of the vesl-1 gene, which also encodes the long form of the Vesl protein (Vesl-1L). Vesl-1L is a postsynaptic scaffolding protein that binds to and modulates the metabotropic glutamate receptor 1/5 (mGluR1/5), the IP 3 receptor, and the ryanodine receptor. Vesl-1 null mutant mice show abnormal behavior, which includes anxiety-and depression-related behaviors, and an increase in cocaine-induced locomotion; however, the function of the short form of Vesl in behavior is poorly understood because of the lack of short-form-specific knockout mice.

Suppression of a Neocortical Potassium Channel Activity by Intracellular Amyloid-β and Its Rescue with Homer1a

“…We examined actions of A␤ in wild-type mice and H1aKO mice, which are so designed that their neurons fail to express Homer1a specifically but not Homer1b/c, the longer splice variant of Homer1 (Inoue et al, 2009). By varying stimulation parameters, we first attempted in mice to reproduce the spike broadening shown in rats so far.…”

“…All experiments were performed in accordance with the guiding principle of the Physiological Society of Japan and with the approval of the Animal Care Committee of Kanazawa Medical University. Wistar rats [postnatal day 16 (P16) to P18], C57BL/6 wild mice (P16 -P19), Homer1a knock-out mice (H1aKO mice; P16 -P19) (Inoue et al, 2009), 4-month-old 3xTg mice (Oddo et al, 2003), and 3xTg mice at P16 -P18 (3xTgj) were used. Animals of either sex were decapitated under ether anesthesia.…”

Homer-1a immediate early gene expression correlates with better cognitive performance in aging

“…Furthermore, Homer-1a knockout mice have been shown to be critical for long-term fear memory formation (Inoue et al 2009). In contrast, mice overexpressing Homer-1a selectively and inducibly in striatal medium spiny neurons showed deficits in motor learning and performance as well as drug-induced stereotypy (Tappe and Kuner 2006).…”

Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review

“…Increased HOMER1 knockout mice also showed somatic growth retardation, poor motor coordination, enhanced sensory reactivity, learning deficits and increased aggression in social interaction 218 Overexpression of HOMER1 in knockout mice reverted the cognitive and behavioural impairments 217 Exposure to novel environments upregulated HOMER1 mRNA in the hippocampus of rats 219 Methamphetamine or cocaine administration upregulated HOMER1 mRNA in the neocortex of rats 220 LSD or PCP administration upregulated HOMER1 mRNA in the PFC of rats 221,222 10Ketamine increased HOMER1 mRNA in the cortical regions, striatum and nucleus accumbens of rats 195,223 Antipsychotics (haloperidol, olanzapine or clozapine) induced an increment of Homer1 protein expression in the cortex, the striatum, the caudate-putamen or nucleus accumbens of rats 107,[224][225][226][227][228] de Bartolomeis et al 107 Matosin et al 189 de Bartolomeis et al 195 Leber et al 213 Inoue et al 214 Gerstein et al 215 Szumlinski et al 216 Lominac et al 217 Jaubert et al 218 Vazdarjanova et al 219 Fujiyama et al 220 Cochran et al 221 Nichols et al 222 Iasevoli et al 223 Iasevoli et al 224 Iasevoli et al 225 Ambesi-Impiombato et al 226 Polese et al 227 Tomasetti et al …”