Thresholds for synaptic activation of transcription factors in hippocampus: correlation with long-term enhancement

Abstract

Recent studies suggest a role for rapid induction of transcription factors in stimulus-induced neuronal plasticity in the mammalian brain. Synaptic activation of transcription factors has been analyzed in the hippocampus using the long-term potentiation or enhancement (LTP/LTE) paradigm. Using this approach, several studies have identified transcription factors that are induced in hippocampal granule cells by NMDA receptor-dependent mechanisms; however, the link between long-term plasticity and activation of these genes has been called into question by reports suggesting that the thresholds for LTE and gene activation differ. To address this issue, we have used a chronic in vivo recording technique to monitor mRNA responses of several transcription factor genes to two different patterns of LTE-inducing electrical stimulation of entorhinal cortical afferents to hippocampus. One pattern consisted of 10 repetitions of a 20 or 25 msec train of pulses at 400 Hz (80 or 100 pulses total). This "10-train" pattern has been used in previous studies of LTE and produces robust synaptic enhancement lasting at least 3 d (Barnes, 1979). The other stimulation pattern consisted of 50 repetitions of a 20 msec train delivered at 400 Hz (400 pulses total), which is similar to parameters used in other studies reporting induction of c-fos in association with LTE (Dragunow et al., 1989; Jeffery et al., 1990; Abraham et al., 1992). Our results indicate that expression of zif268, monitored by in situ hybridization and immunostaining, is strongly induced by the 10-train stimulus pattern to levels similar to those induced by seizure activity. JunB mRNA levels are also modestly increased by the 10-train stimulus pattern; however, increases in JunB immunostaining were not detected. Neither c-fos nor c-jun mRNA were detectably induced by this stimulus. In contrast, the 50-train stimulus pattern resulted in a robust induction of c-fos and c-jun mRNA, in addition to zif268 and junB. Transcription factor responses to either stimulus pattern were blocked by the noncompetitive NMDA receptor antagonist MK-801. Identical transcription factor responses were observed in adult (6-12-month-old) and aged (23-26-month-old) rats, suggesting that synaptic mechanisms involved in these responses are preserved in aged animals. Analysis of LTE following either the 10- or 50-train stimulus patterns revealed identical magnitudes of initial induction and decay kinetics (approximately 3 d) and indicates that the 10-train stimulus pattern is sufficient to produce maximal synaptic enhancement.(ABSTRACT TRUNCATED AT 400 WORDS)

Brief Social Defeat Stress: Long Lasting Effects on Cocaine Taking During a Binge and Zif268 mRNA Expression in the Amygdala and Prefrontal Cortex

“…For example, the reconsolidation of long-term memory is dependent on zif268, but not other transcription factors (Lee et al, 2004). Likewise, cfos expression is not correlated as tightly as zif268 expression with the synaptic enhancement of hippocampal cells in response to electrical stimulation (Worley et al, 1993). Although environmental stimuli can clearly regulate c-fos and zif268 expression, additional experiments are necessary to clarify the divergent functional roles of these IEGs within the same cell groups in response to stressful provocations.…”

Calcium Controls Gene Expression via Three Distinct Pathways That Can Function Independently of the Ras/Mitogen-Activated Protein Kinases (ERKs) Signaling Cascade

“…In contrast, SRE-dependent transcription (discussed below) can be stimulated independently of increases in nuclear calcium by a rise in cytoplasmic calcium (Hardingham et al, 1997). This may explain why the zif/268 gene, which contains several SREs in its promoter (Changelian et al, 1989;Christy et al, 1989), is activated even with moderate LTP-inducing stimuli that may not increase the nuclear calcium concentration (Cole et al, 1989;Wisden et al, 1990;Worley et al, 1993). The molecular mechanisms controlled by nuclear calcium may involve CaM kinase IV.…”

Relapse to cocaine-seeking increases activity-regulated gene expression differentially in the striatum and cerebral cortex of rats following short or long periods of abstinence

“…Moreover, cocaine-induced behavioral sensitization and conditioned place preference are absent in zif/268 knockout mice (Valjent et al 2006). However, because IEGs are regulated by complex neurotransmitter interactions, they are distinguished by differences in their induction thresholds and responses to stimuli (Worley et al 1993;West et al 2002). Thus, in this study, alterations in c-fos, zif/268, and arc mRNA expression were used to identify activation of associative and sensory-motor cortices as well as their striatal targets in response to a cocaine-associated context after a short or long period of abstinence.…”