Seizure-Induced Arc mRNA Expression Thresholds in Rat Hippocampus and Perirhinal Cortex

Abstract

Immediate-early genes (IEGs) are rapidly and transiently induced following excitatory neuronal activity including maximal electroconvulsive shock treatment (ECT). The rapid RNA response can be blocked by the sodium channel antagonist tetrodotoxin (TTX), without blocking seizures, indicating a role for electrical stimulation in electroconvulsive shock-induced mRNA responses. In behaving animals, Arc mRNA is selectively transcribed following patterned neuronal activity and rapidly trafficked to dendrites where it preferentially accumulates at active synapses for local translation. Here we examined whether there is a relationship between the current intensities that elicit seizures and the threshold for Arc mRNA transcription in the rat hippocampus and perirhinal cortex (PRC). Animals received ECT of varying current intensities (0, 20, 40 65, 77 and 85 mA) and were sacrificed 5 min later. While significantly more CA1, CA3 and perirhinal pyramidal cells expressed Arc at the lowest stimulus intensity compared to granule cells, there was an abrupt threshold transition that occurred in all four regions at 77 mA. This precise threshold for Arc expression in all temporal lobe neurons examined may involve regulation of the calcium-dependent mechanisms that are upstream to activity-dependent IEG transcription.

Expression of the Neuronal tRNA n-Tr20 Regulates Synaptic Transmission and Seizure Susceptibility

“…The increased seizure threshold observed in n-Tr20 mutant mice suggests that the balance of excitation and inhibition may be altered, as seen in models of epilepsy and other neurological disorders (Lee et al, 2017). Multiple brain regions, including the hippocampal formation, have been implicated in seizure activity (Barton et al, 2001;Chawla et al, 2018). Due to its well-defined circuitry and the widespread expression of n-Tr20 therein, we examined the effect of n-Tr20 loss on synaptic transmission in the CA1 region of the hippocampus.…”

Electroconvulsive Shock Does Not Impair the Reconsolidation of Cued and Contextual Pavlovian Threat Memory

“…The tonic-clonic seizure induced by ECS results in brain-wide neural activation that can induce large-scale synaptic modification. Consistent with this, a single administration of ECS has been shown to induce gene expression and morphological changes in neurons across brain regions, including the hippocampus and frontal cortex [ 29 , 44 , 45 , 46 , 47 , 48 , 49 ]—two areas critical for fear learning and memory modification via reconsolidation and extinction [ 28 , 50 ]. It is not surprising that ECS can disrupt memory processes; however, the exact mechanism by which this occurs is unclear.…”

Orexin-A promotes neurite outgrowth and induces activity-regulated cytoskeleton associated protein (Arc) upregulation in SH-SY5Y cells

“…In this study, we showed that Ox-A, in addition to increasing the number of cells with longer neurites, also increased the amount of Arc protein. Arc is highly expressed in several situations of synaptic plasticity, including acute administration of addictive drugs, e.g., morphine [42], cocaine [43], and methamphetamine [44] alcohol [45], stress [46] seizure [47], and LTP [48]. These ndings are relevant considering that Ox-A modulates reward-processing, promotes drug-seeking behavior, improves memory and learning [49].…”