Persistent neural activity regulates Arc/Arg3.1 transcription in the dentate gyrus.
ABSTRACT The activity-regulated cytoskeleton-associated gene (Arc, also known as Arg3.1) is an effector immediate-early gene rapidly induced by strong neural activity. Although a number of studies have revealed significant functions of Arc and Arc has come into widespread use as a neural activity marker in behavioral studies, the mechanisms regulating Arc transcription remain unclear. Here, we examined the conditions of Arc transcription in acute slices of dentate gyrus. Surprisingly, kainic acid (1 μM to 10 mM) application to slices did not induce Arc transcription, although intraperitoneal injection of kainic acid (20 mg/kg) induced robust Arc transcription. No types of high-frequency stimulation examined induced Arc transcription in acute slices. These findings indicate that Arc transcription is dramatically suppressed in acute slices of the dentate gyrus, in which background neural activity is markedly reduced. Burst stimulation increased the number of Arc-expressing cells in the presence of picrotoxin, in which excitation was maintained even after the end of stimulation. Moreover, the involvement of background neural activity in Arc transcription was tested by application of carbachol, a muscarinic receptor agonist. Carbachol also increased the number of Arc-expressing cells, which was blocked by atropine, a muscarinic receptor antagonist. Taken together, these findings suggest that persistent background activity is critical for Arc transcription.
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ABSTRACT: The morphology of neurons in the "hilar region" of the hippocampus (fields CA3c and CA4 of Lorente de Nó, '34) was analyzed with several variants of the Golgi technique. Hippocampi were dissected from the brains of 28-day-old rats, fixed and impregnated by immersion, and sectioned perpendicular to the long axis. Based on the resident cell types, aspects of the neuropil, and published data related to afferent termination, the area under study was divided into four zones. At least 21 cell types were observed throughout these zones, several of which had not previously been described. Many cells in this area exhibited an impressive number and variety of dendritic and axonal appendages, including spines on the proximal portion of some axons. The close apposition of fibers to these axonal spines suggested the possibility of axo-axonal interactions. The influence of dentate granule cells, through their mossy fibers, on the synaptic economy of the "hilar region" was found to be more extensive than previously reported. Mossy fibers appeared to terminate on the dendrites of several types of non-pyramidal cells, which bear no thorny excrescences, by means of thin filiform extensions which emanate from the mossy fiber expansions and by means of thin mossy fiber collaterals which are devoid of typical expansions. Consideration is given to a long-standing debate as to whether the deep "hilar region" (CA4 of Lorente de Nó, '34, hilus of the fascia dentata of Blackstad, '56) is related more to the hippocampus or to the fascia dentata and it is concluded that the deep hilar region is an area of mergence of the polymorphic zones of these two cortical structures. The results of the present study do not support the proposition that the deep hilar region is an extension of the pyramidal layer of the hippocampus as suggested by Lorente de Nó ('34), and thus CA4 is a misnomer. Rather, the cells in this area are most closely related to the fascia dentata and should thus be considered to lie in the polymorphic zone of "area dentata" as proposed initially by Blackstad ('56).The Journal of Comparative Neurology 01/1979; 182(4 Pt 2):851-914. · 3.66 Impact Factor
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ABSTRACT: 1. The hypothesis that dentate hilar "mossy" cells are excitatory was tested by simultaneous intracellular recording in rat hippocampal slices. Mossy cells were recorded simultaneously with their potential targets, granule cells and interneurons. The gamma-amino-butyric acid-A (GABAA) receptor antagonist bicuculline was used in most experiments to block the normally strong inhibitory inputs to granule cells that could mask excitatory effects of mossy cells. Some cells were recorded with electrodes containing the marker Neurobiotin so that their identity could be confirmed morphologically. 2. A mossy cell action potential was immediately followed by a brief depolarization in a granule cell in 20 of 1,316 pairs (1.5%) that were recorded in the presence of bicuculline. The mean amplitude of depolarizations was 1.99 +/- 0.24 (SE) mV when the postsynaptic membrane potential was -55 to -65 mV. Depolarizations could trigger an action potential if the granule cell was depolarized from its resting potential so that its membrane potential was -50 to -60 mV. These data suggest that mossy cells excite granule cells monosynaptically. 3. Monosynaptic excitation of an interneuron by a mossy cell was recorded in 4 of 47 (8.5%) simultaneously recorded mossy cells and interneurons, also in the presence of bicuculline. The mean interneuron depolarization was 1.64 +/- 0.29 mV when the interneuron membrane potential was approximately -60 mV. When an interneuron was at its resting potential (-52 to -63 mV), action potentials were often triggered by the depolarizations. 4. Without bicuculline present, mossy cells had no apparent monosynaptic effects on granule cells, as has been previously reported. However, effects that appeared to be polysynaptic were observed in 5 of 92 pairs (5.4%). Specifically, a small, brief hyperpolarization occurred in granule cells 2.5-7.3 ms after the peak of a mossy cell action potential. Given the results indicating that mossy cells excite interneurons, and the long latency to onset of the hyperpolarization, one possible explanation for the hyperpolarization is that mossy cells excited interneurons that inhibited granule cells. 5. The results suggest that mossy cells are excitatory neurons. In addition, mossy cells appear to innervate both granule cells and interneurons that are located within several hundred micrometers of the mossy cell soma. The only detectable effect on granule cells in this area under normal conditions appears to be disynaptic and inhibitory. However, when GABAA-receptor-mediated inhibition is blocked, monosynaptic excitation of granule cells by mossy cells can be detected.Journal of Neurophysiology 08/1995; 74(1):179-94. · 3.30 Impact Factor
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ABSTRACT: Trans-synaptic activation of gene expression is linked to long-term plastic adaptations in the nervous system. To examine the molecular program induced by synaptic activity, we have employed molecular cloning techniques to identify an immediate early gene that is rapidly induced in the brain. We here report the entire nucleotide sequence of the cDNA, which encodes an open reading frame of 396 amino acids. Within the hippocampus, constitutive expression was low. Basal levels of expression in the cortex were high but can be markedly reduced by blockade of N-methyl-D-aspartate receptors. By contrast, synaptic activity induced by convulsive seizures increased mRNA levels in neurons of the cortex and hippocampus. High-frequency stimulation of the perforant path resulted in long-term potentiation and a spatially confined dramatic increase in the level of mRNA in the granule cells of the ipsilateral dentate gyrus. Transcripts were localized to the soma and to the dendrites of the granule cells. The dendritic localization of the transcripts offers the potential for local synthesis of the protein at activated postsynaptic sites and may underlie synapse-specific modifications during long-term plastic events.Proceedings of the National Academy of Sciences 07/1995; 92(12):5734-8. · 9.74 Impact Factor