Long-term potentiation in the dentate gyrus is not linked to increased extracellular glutamate concentration.
(9/1453)
Long-term potentiation (LTP) of excitatory transmission is a likely candidate for the encoding and storage of information in the mammalian brain. There is a general agreement that LTP involves an increase in synaptic strength, but the mechanisms underlying this persistent change are unclear and controversial. Synaptic efficacy may be enhanced because more transmitter glutamate is released or because postsynaptic responsiveness increases or both. The purpose of this study was to examine whether increased extracellular glutamate concentration was associated with the robust and well-characterized LTP that can be induced in the rat dentate gyrus. To favor the detection of any putative change in extracellular glutamate associated with LTP, our experimental strategy included the following features. 1) Two separate series of experiments were carried out with animals under pentobarbital or urethan anesthesia; 2) changes in extracellular concentration of glutamate were monitored continuously by microdialysis coupled to enzyme amperometry; and 3) dialysate glutamate levels and changes in the slope of excitatory postsynaptic potential evoked by activation of the perforant path were recorded precisely at the same site. Tetanic stimulation of the perforant path increased persistently test-evoked responses in the dentate gyrus (by 19 and 14% in barbiturate and urethan group, respectively), but there was no glutamate change either during or after LTP induction and no indication of increased glutamate efflux when low-frequency stimulation was applied. The results do not rule out a possible contribution of enhanced glutamate exocytosis to LTP induction and/or maintenance because such a presynaptic change may not be detectable extracellularly. However, our findings and other data supporting the notion that neurotransmitter glutamate may hardly leak out of the synaptic cleft conflict with the hypothesis that LTP could also involve a broad synaptic spillover of glutamate. (+info)
Granule cells in aging rats are sexually dimorphic in their response to estradiol.
(10/1453)
Normal aging comprises cognitive decline, including deterioration of memory. It has been suggested that this decline in memory is sexually dimorphic because of the cessation in gonadal steroid secretion that occurs during reproductive aging in female, but not male, mammals. We wondered whether neurons in brain regions associated with learning and memory underwent morphological changes that were dimorphic as well and whether cessation of the secretion of gonadal steroids influenced these morphological changes. To explore these questions, we deprived and restored estrogens to young and old gonadectomized females and males and studied the morphology of dentate granule cells by intracellular dye filling in a lightly fixed slice preparation. We found the following: (1) Aged female dentate granule cells deprived of gonadal steroids long-term have a paucity of dendritic spines compared with young females deprived short-term; however, aged male dentate granule cells deprived of gonadal steroids long-term have no decrease in dendritic spines compared with young males deprived short-term. (2) Aged female dentate granule cells with long-term estrogen replacement at either high or low levels still had a decline in spine density. (3) Aged female dentate granule cells with short-term estradiol replacement had spine density increased to levels normally observed in young adults, whereas aged males with short-term estradiol replacement had decreased spine density. These data suggest that the response of rat dentate granule cells to aging and estradiol is sexually dimorphic and that, in females, the responsiveness of granule cells depends on the temporal pattern of estradiol replacement. (+info)
A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory.
(11/1453)
Behavioral, biophysical, and pharmacological studies have implicated the hippocampus in the formation and storage of spatial memory. However, the molecular mechanisms underlying long-term spatial memory are poorly understood. In this study, we show that mitogen-activated protein kinase (MAPK, also called ERK) is activated in the dorsal, but not the ventral, hippocampus of rats after training in a spatial memory task, the Morris water maze. The activation was expressed as enhanced phosphorylation of MAPK in the pyramidal neurons of the CA1/CA2 subfield. In contrast, no increase in the percentage of phospho-MAPK-positive cells was detected in either the CA3 subfield or the dentate gyrus. The enhanced phosphorylation was observed only after multiple training trials but not after a single trial or after multiple trials in which the location of the target platform was randomly changed between each trial. Inhibition of the MAPK/ERK cascade in dorsal hippocampi did not impair acquisition, but blocked the formation of long-term spatial memory. In contrast, intrahippocampal infusion of SB203580, a specific inhibitor of the stress-activated MAPK (p38 MAPK), did not interfere with memory storage. These results demonstrate a MAPK-mediated cellular event in the CA1/CA2 subfields of the dorsal hippocampus that is critical for long-term spatial memory. (+info)
Complex behavioral strategy and reversal learning in the water maze without NMDA receptor-dependent long-term potentiation.
(12/1453)
Successful performance of the water maze task requires that rats learn complex behavioral strategies for swimming in a pool of water, searching for and interacting with a hidden platform before its spatial location can be learned. To evaluate whether NMDA receptor-dependent long-term potentiation (NMDA-LTP) is required for learning the required behavioral strategies, rats with NMDA-LTP blocked by systemic pharmacological treatment were trained in the behavioral strategies using simplified and stepwise training methods. Despite the blockade of NMDA-LTP in the dentate gyrus and hippocampal area CA1, rats learned the required behavioral strategies and used them to learn both initial and reversed platform locations. This is the first evaluation of the role of NMDA-LTP specifically in behavioral strategy learning. Although hippocampal NMDA-LTP might contribute to the water maze task, this form of LTP is not essential for learning complex behavioral strategies or multiple hidden platform locations. (+info)
Continuation of neurogenesis in the hippocampus of the adult macaque monkey.
(13/1453)
We present evidence for continuous generation of neurons, oligodendrocytes, and astrocytes in the hippocampal dentate gyrus of adult macaque monkeys, using immunohistochemical double labeling for bromodeoxyuridine and cell-type-specific markers. We estimate that the relative rate of neurogenesis is approximately 10 times less than that reported in the adult rodent dentate gyrus. Nevertheless, the generation of these three cell types in a discreet brain region suggests that a multipotent neural stem cell may be retained in the adult primate hippocampus. This demonstration of adult neurogenesis in nonhuman Old World primates-with their phylogenetic proximity to humans, long life spans, and elaborate cognitive abilities-establishes the macaque as an unexcelled animal model to experimentally investigate issues of neurogenesis in humans and offers new insights into its significance in the adult brain. (+info)
Physiological properties of GABAA receptors from acutely dissociated rat dentate granule cells.
(14/1453)
Physiological properties of GABAA receptors from acutely dissociated rat dentate granule cells. Study of fast, GABAA receptor-mediated, inhibitory postsynaptic currents (IPSCs) in hippocampal dentate granule cells has suggested that properties of GABAA receptors influence the amplitude and time course of the IPSCs. This study describes the physiological properties of GABAA receptors present on hippocampal dentate granule cells acutely isolated from 18- to 35-day-old rats. Rapid application of 1 mM GABA to outside-out macropatches excised from granule cells produced GABAA receptor currents with rapid rise time and biexponential decay of current after removal of GABA. After activation, granule cell GABAA receptor currents desensitized incompletely. During a 400-ms application of 1 mM GABA, peak current only desensitized approximately 40%. In symmetrical chloride solutions there was no outward rectification of whole cell current. Activation rates and peak currents elicited by rapid application of GABA to macropatches were also similar at positive and negative holding potentials. However, deactivation of GABAA receptor currents was slower at positive holding potentials. When whole cell currents were recorded without ATP in the pipette, current run-down was not apparent for 30 min in 50% of neurons, but run-down appeared to start soon after access was established in the remaining neurons. When 2 mM ATP was included in the recording pipette no run-down was apparent in 30 min of recording. The efficacy and potency of GABA were lower in cells recorded with no ATP in the pipette and during run-down compared with those recorded with 2 mM ATP and no run-down. (+info)
Expression of preproopiomelanocortin mRNA and preprodynorphin mRNA in brain of spontaneously hypertensive rats.
(15/1453)
AIM: To compare the expressions of prepropiomelanocortin (POMC) mRNA and preprodynorphin (PPD) mRNA between 16-wk-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY). METHODS: The expression of POMC mRNA and PPD mRNA were detected with nonradioactive in situ hybridization by digoxigenin-labeled RNA probe. RESULTS: POMC mRNA mainly was expressed in arcuate nucleus, compared with WKY, SHR had higher level of POMC mRNA (542). PPD mRNA was found in hippocampus, hypothalamus, central gray, nucleus of the solitary tract (NTS), and thoracic spinal cord (T4-T6). Compared with WKY, PPD mRNA level of SHR decreased in dentate gyrus (2342), NTS (381), and medial preoptic area (467); no difference was observed in arcuate nucleus (263), thoracic spinal cord (750-1800) and CA1, CA2, CA3 of hippocampus (1674, 2014, 2626). CONCLUSION: Increase of POMC mRNA in arcuate nucleus and decrease of PPD mRNA in dentate gyrus of SHR may be associated with the genesis of spontaneous hypertension. (+info)
Control of hippocampal morphogenesis and neuronal differentiation by the LIM homeobox gene Lhx5.
(16/1453)
The mammalian hippocampus contains the neural circuitry that is crucial for cognitive functions such as learning and memory. The development of such circuitry is dependent on the generation and correct placement of the appropriate number and types of neurons. Mice lacking function of the LIM homeobox gene Lhx5 showed a defect in hippocampus development. Hippocampal neural precursor cells were specified and proliferated, but many of them failed to either exit the cell cycle or to differentiate and migrate properly. Lhx5 is therefore essential for the regulation of precursor cell proliferation and the control of neuronal differentiation and migration during hippocampal development. (+info)