Extracellular recordings in the colchicine-lesioned rat dentate gyrus following transplants of fetal dentate gyrus and CA1 hippocampal subfield tissue

Grafts of fetal dentate gyrus (DG) and CA1 hippocampal subfield tissue were extruded into the dentate gyri of adult male Sprague-Dawley rats, 7-10 days after lesioning the granule cells with colchicine (0.06 microliter of 7 mg/ml solution at each of 5 sites/hippocampus). Graft area-host and host-graft area connectivities were investigated 4-6 months post-transplantation by recoding extracellular evoked response in hippocampal slice preparations. Following stimulation of the host mid-molecular layer, evoked field potential responses, showing considerable variation, were recorded in both types of graft. Evoked responses in the lesioned DG without grafts were recorded in very few slices. Stimulation of the area of DG tissue grafts occasionally evoked responses in the host CA3/CA4 and there was no evidence for CA1 graft area-CA3/CA4 connectivity; stimulation of DG and CA1 graft areas occasionally evoked responses in the host CA1. Responses in the area of both DG and CA1 grafts supported short-term potentiation following stimulation of the host mid-molecular layer but only DG graft areas supported long-term potentiation of the population spike amplitude. In the area of both types of transplant a tonic bicuculline-sensitive inhibition was present and paired-pulse stimulation paradigms provided some evidence for inhibition. It is possible that responses recorded within the area of grafted tissue to stimulation of the host are attributable to host-graft connectivity and similarly, responses recorded in the host to stimulation of the area of the graft may be attributable to graft-host connectivity. Only DG graft areas received host inputs which were capable of sustaining a long-term potentiation and establishing efferent contacts with the host CA3/CA4 subfield, suggesting that these would be more likely than CA1 grafts to reinstate normal functional circuitry.     

Activity-dependent response depression in rat hippocampal CA1 pyramidal neurons in vitro

1. A gradual and prolonged decrease of the response, termed here "depression," evoked by repeated activation with transmembrane current stimuli was analyzed in rat CA1 hippocampal pyramidal cells under single-electrode current clamp by the use of the in vitro slice technique. 2. Depression was induced by 2-s duration 0.3- to 0.7-nA current pulses presented as a sequence of 12 stimuli at 3- to 60-s intervals. Sinusoidal currents (0.5-1.0 nA) at 5-Hz or 200-ms pulses repeated at 0.3-0.5/s, which may be more natural stimulations, also induced depression. 3. Depression outlasted stimulation up to 170 s in all cells tested. The initial high rate spike burst changed little (< 20%), whereas the lower rate adapted response decreased markedly (> 40%). Thus neurons increased their rate of adaptation. The afterhyperpolarizations following pulse-evoked responses increased in duration and amplitude with depression. There were input resistance (Rin) reductions at depolarized membrane potentials and during pulses. However, Rin reductions were considerably smaller or altogether absent late during interpulse intervals. Sub-threshold current stimuli were ineffective, indicating that spike activity was necessary to elicit depression. 4. Depression was 1) insensitive to the toxin omega-Agatoxin-IVA (omega-Aga-IVA; 0.5 microM), which blocked synaptic transmission, revealing a key involvement of intrinsic properties and little if any synaptic participation; 2) insensitive to 4-aminopyrydine (2.00-4.00 mM), which greatly enhanced excitatory and inhibitory synaptic efficacy, again suggesting little synaptic involvement and a principal postsynaptic participation, and no participation of the K(+)-mediated currents IA and ID; 3) abolished by carbamalcholine (5.0-20.0 microM)- an effect blocked by atropine (1.0-10.0 microM)- and reduced by Ca(2+)-free solutions, and by intracellular injection of the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), suggesting that Ca(2+)-dependent K(+)-mediated currents are key factors, with a less important participation of the K(+)-mediated IM current. 5. We conclude that depression was due to activity-dependent modifications in intrinsic properties, with little if any synaptic participation. Depression may be functionally significant because it was induced by potentially natural stimulations. A model is proposed that accounts for the main traits of depression. In the model, depression was induced by a gradual decline of the speed at which Ca2+ was buffered intracellularly; an increase in the IK(Ca)S activation rate constant also simulated depression.     

Evidence from simultaneous intracellular recordings in rat hippocampal slices that area CA3 pyramidal cells innervate dentate hilar mossy cells

1. Simultaneous intracellular recordings of area CA3 pyramidal cells and dentate hilar "mossy" cells were made in rat hippocampal slices to test the hypothesis that area CA3 pyramidal cells excite mossy cells monosynaptically. Mossy cells and pyramidal cells were differentiated by location and electrophysiological characteristics. When cells were impaled near the border of area CA3 and the hilus, their identity was confirmed morphologically after injection of the marker Neurobiotin. 2. Evidence for monosynaptic excitation of a mossy cell by a pyramidal cell was obtained in 7 of 481 (1.4%) paired recordings. In these cases, a pyramidal cell action potential was followed immediately by a 0.40 to 6.75 (mean, 2.26) mV depolarization in the simultaneously recorded mossy cell (mossy cell membrane potentials, -60 to -70 mV). Given that pyramidal cells used an excitatory amino acid as a neurotransmitter (Cotman and Nadler 1987; Ottersen and Storm-Mathisen 1987) and recordings were made in the presence of the GABAA receptor antagonist bicuculline (25 microM), it is likely that the depolarizations were unitary excitatory postsynaptic potentials (EPSPs). 3. Unitary EPSPs of mossy cells were prone to apparent "failure." The probability of failure was extremely high (up to 0.72; mean = 0.48) if the effects of all presynaptic action potentials were examined, including action potentials triggered inadvertently during other spontaneous EPSPs of the mossy cell. Probability of failure was relatively low (as low as 0; mean = 0.24) if action potentials that occurred during spontaneous activity of the mossy cell were excluded. These data suggest that unitary EPSPs produced by pyramidal cells are strongly affected by concurrent synaptic inputs to the mossy cell. 4. Unitary EPSPs were not clearly affected by manipulation of the mossy cell's membrane potential. This is consistent with the recent report that area CA3 pyramidal cells innervate distal dendrites of mossy cells (Kunkel et al. 1993). Such a distal location also may contribute to the high incidence of apparent failures. 5. Characteristics of unitary EPSPs generated by pyramidal cells were compared with the properties of the unitary EPSPs produced by granule cells. In two slices, pyramidal cell and granule cell inputs to the same mossy cell were compared. In other slices, inputs to different mossy cells were compared. In all experiments, unitary EPSPs produced by granule cells were larger in amplitude but similar in time course to unitary EPSPs produced by pyramidal cells. Probability of failure was lower and paired-pulse facilitation more common among EPSPs triggered by granule cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

GABAB receptor-mediated inhibition of tetrodotoxin-resistant GABA release in rodent hippocampal CA1 pyramidal cells

Tight-seal whole-cell recordings from CA1 pyramidal cells of rodent hippocampus were performed to study GABAB receptor-mediated inhibition of tetrodotoxin (TTX)-resistant IP-SCs. IPSCs were recorded in the presence of TTX and glutamate receptor antagonists. (R)-(-)-baclofen reduced the frequency of TTX-resistant IPSCs by a presynaptic action. The inhibition by (R)-(-)-baclofen was concentration-dependent, was not mimicked by the less effective enantiomer (S)-(+)-baclofen, and was blocked by the GABAB receptor antagonist CGP 55845A, suggesting a specific effect on GABAB receptors. The inhibition persisted in the presence of the Ca2+ channel blocker Cd2+. There was no requirement for an activation of K+ conductances by (R)-(-)-baclofen, because the inhibition of TTX-resistant IPSCs persisted in Ba2+ and Cd2+. Because the time courses of TTX-resistant IPSCs were not changed by (R)-(-)-baclofen, there was no evidence for a selective inhibition of quantal release from a subgroup of GABAergic terminals. (R)-(-)-baclofen reduced the frequency of TTX-resistant IPSCs in guinea pigs and Wistar rats, whereas the inhibition was much smaller in Sprague Dawley rats. In Cd2+ and Ba2+, beta-phorbol-12,13-dibutyrate and forskolin enhanced the frequency of TTX-resistant IPSCs. Only beta-phorbol-12, 13-dibutyrate reduced the inhibition by (R)-(-)-baclofen. We conclude that GABAB receptors inhibit TTX-resistant GABA release through a mechanism independent from the well known effects on Ca2+ or K+ channels. The inhibition of quantal GABA release can be reduced by an activator of protein kinase C.     

Postnatal development and synaptic connections of hilar mossy cells in the hippocampal dentate gyrus of rhesus monkeys

On the basis of the literature findings, the modern ideas about the structure and function of calcium canals of plasmatic and intracellular membranes of the living cells are generalized and systematized. The major electrophysiologic and chemical properties of the main groups and types of potential-controlled and receptor-controlled calcium canals are reviewed. The article gives the classification and nomenclature of the calcium canals as well as the characteristics of different types of calcium antagonists and the cases of their clinical application.     

Long-term and short-term plasticity in the CA1, CA3, and dentate regions of the rat hippocampal slice

Subregions of the rat hippocampal slice were investigated in relation to (a) the presence of long-term potentiation and (b) responsiveness to low-frequency stimulation. Long-term potentiation was observed in CA1, CA3 and dentate. The effect occasionally lasted up to 6 h, developed gradually, and depended upon repeated low-frequency tetani for maximal effect. To low-frequency monosynaptic stimulation, areas CA3 and CA1 exhibit response facilitation whereas the dentate gyrus exhibits response depression. Reponsiveness in all areas was influenced by stimulus frequency. Recovery was rapid in all areas.     

Operative GABAergic inhibition in hippocampal CA1 pyramidal neurons in experimental epilepsy

Patch-clamp recordings of CA1 interneurons and pyramidal cells were performed in hippocampal slices from kainate- or pilocarpine-treated rat models of temporal lobe epilepsy. We report that gamma-aminobutyric acid (GABA)ergic inhibition in pyramidal neurons is still functional in temporal lobe epilepsy because: (i) the frequency of spontaneous GABAergic currents is similar to that of control and (ii) focal electrical stimulation of interneurons evokes a hyperpolarization that prevents the generation of action potentials. In paired recordings of interneurons and pyramidal cells, synchronous interictal activities were recorded. Furthermore, large network-driven GABAergic inhibitory postsynaptic currents were present in pyramidal cells during interictal discharges. The duration of these interictal discharges was increased by the GABA type A antagonist bicuculline. We conclude that GABAergic inhibition is still present and functional in these experimental models and that the principal defect of inhibition does not lie in a complete disconnection of GABAergic interneurons from their glutamatergic inputs.     

Dendritic properties of hippocampal CA1 pyramidal neurons in the rat: intracellular staining in vivo and in vitro

Dendritic morphology and passive cable properties determine many aspects of synaptic integration in complex neurons, together with voltage-dependent membrane conductances. We investigated dendritic properties of CA1 pyramidal neurons intracellularly labeled during in vivo and in vitro physiologic recordings, by using similar intracellular staining and three-dimensional reconstruction techniques. Total dendritic length of the in vivo neurons was similar to that of the in vitro cells. After correction for shrinkage, cell extent in three-dimensional representation was not different between the two groups. Both in vivo and in vitro neurons demonstrated a variable degree of symmetry, with some neurons showing more cylindrical symmetry around the main apical axis, whereas other neurons were more elliptical, with the variation likely due to preparation and preservation conditions. Branch order analysis revealed no difference in the number of branch orders or dendritic complexity. Passive conduction of dendritic signals to the soma in these neurons shows considerable attenuation, particularly with higher frequency signals (such as synaptic potentials compared with steady-state signals), despite a relatively short electrotonic length. Essential aspects of morphometric appearance and complex dendritic integration critical to CA1 pyramidal cell functioning are preserved across neurons defined from the two different hippocampal preparations used in this study.     

Activation of metabotropic glutamate receptors induce differential effects on synaptic transmission in the dentate gyrus and CA1 of the hippocampus in the anaesthetized rat

Activation of ACPD-sensitive metabotropic receptors induced differential effects on synaptic transmission and the induction of LTP in CA1 and the dentate gyrus of the hippocampus i.c.v. injections of (1.S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] induced enduring potentiation of the fEPSP in CA1, which occluded tetanically induced LTP. In contrast, ACPD induced a dose-dependent biphasic effect on the fEPSP in the dentate gyrus, consisting of an initial short lasting potentiation, followed by enduring depression of the response, and blockade of LTP. These two effects are likely to be mediated by two different classes of the receptor as in the dentate gyrus the selective class I agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG) induced sustained potentiation of the fEPSP, whereas the mixed mGluR2 agonist-mGluR1 antagonist, (S)-4-carboxy-3-hydrophenylglycine((S)-4C3H-PG) induced only depression. Increasing the concentration of calcium directly in the dentate gyrus prior to, and in conjunction with, injections of ACPD induced sustained potentiation rather than depression. The differential effects indicate that the second messenger cascades the subtypes of receptors are linked with, mediate different forms of synaptic plasticity within the hippocampus and have important implications for their role in learning.     

Corticosteroids alter 5-hydroxytryptamine1A receptor-effector pathway in hippocampal subfield CA3 pyramidal cells

Corticosteroids influence neuron activity in the hippocampus through the activation of mineralocorticoid and glucocorticoid receptors. For example, corticosteroids modulate the responses elicited by the activation of several different neurotransmitter receptors on hippocampal pyramidal cells. However, the effects of corticosteroids on the serotonin (5-HT) receptors systems in subfield CA3 are not completely known. Therefore, we used single-electrode voltage clamp techniques to examine the actions of chronic corticosteroid treatment on the 5-HT1A receptor-effector pathway in rat hippocampal subfield CA3 pyramidal cells. Activation of the 5-HT1A receptor increases the conductance of an inward rectifying potassium channel, increasing outward current. The treatment groups used in this investigation were: adrenalectomy, selective mineralcorticoid receptor activation with aldosterone, mineralcorticoid receptor and glucocorticoid receptor activation with high levels of corticosterone and SHAM. Corticosteroids altered the characteristics of the 5-HT concentration-response curve for the 5-HT1A receptor. The effective concentration at 50% of maximum value was smaller in cells from the adrenalectomy treatment group compared to the other treatment groups. The maximum response was smaller in cells from the high corticosterone treatment group compared to SHAM and adrenalectomy treatment group animals. G protein function was also altered by corticosterone treatment. Less current was elicited by guanosine 5'-0-13-thiotriphosphate in cells from the high corticosterone treatment group compared to the other treatment groups and in cells from the SHAM treatment group compared to adrenalectomy treatment group animals. Corticosteroid treatment did not alter the current-voltage relationship, the conductance or the reversal potential of the potassium current linked to the 5-HT1A receptor. We conclude that corticosteroids alter the 5-HT1A receptor-mediated-response in hippocampal subfield CA3 neurons at site(s) downstream of the receptor.     

Degeneration of hippocampal CA3 pyramidal cells induced by intraventricular kainic acid

Degeneration of hippocampal CA3 pyramidal cells was investigated by light and electron microscopy after intraventricular injection of the potent convulsant, kainic acid. Electron microscopy revealed evidence of pyramidal cell degeneration within one hour. The earliest degenerative changes were confined to the cell body and proximal dendritic shafts. These included an increased incidence of lysosomal structures, deformation of the perikaryal and nuclear outlines, some increase in background electron density, and dilation of the cisternae of the endoplasmic reticulum accompanied by detachment of polyribosomes. Within the next few hours the pyramidal cells atrophied and became electron dense. Then these cells became electron lucent once more as ribosomes disappeared and their membranes and organelles broke up and disintegrated. Light microscopic changes correlated with these ultrastructural observations. The dendritic spines and the initial portion of the dendritic shaft became electron dense within four hours and degenerated rapidly, whereas the intermediate segment of the dendrites swelled moderately and became more electron lucent. No degenerative changes were evident in pyramidal cell axons and boutons until one day after kainic acid treatment. Less than one hour after kainic acid administration, astrocytes in the CA3 area swelled, initially in the vicinity of the cell body and mossy fiber layers. It is suggested that the paroxysmal discharges initiated in CA3 pyramidal cells by kainic acid served as the stimulus for this response. Phagocytosis commenced between one and three days after kainic acid administration, but remained incomplete at survival times of 6-8 weeks. Astrocytes, microglia, and probably oligodendroglia phagocytized the degenerating material. These results point to the pyramidal cell body and possibly also the dendritic spines as primary targets of kainic acid neurotoxicity. In conjunction with other data, they support the view that lesions made by intraventricular kainic acid can serve as models of epileptic brain damage.     

Lateral entorhinal, perirhinal, and amygdala-entorhinal transition projections to hippocampal CA1 and dentate gyrus in the rat: a current source density study

In the health management of bone, of most importance is how to spend the period until peak bone mass, that is appropriate self management for bone health. Therefore, we evaluated the effects of physical characteristics and dietary habits on the bone mineral density (BMD) of the second metacarpal bone (sigma GS/D: BMD) by the digital image processing method (DIP) in 197 healthy adolescent girls (Japanese students at a junior high school, aged 12-15 y), an important period of physical and bone growth. Concerning the physical characteristics of the subjects according to age group, body height in each age group was higher than the standard values for Japanese according to age, but body weights in the 14-year-old and 15-year-old groups were significantly lower than the standard values for Japanese. Compared with the standard BMD values for Japanese according to age, BMD in the subjects was high in the 12-year-old, 13-year-old and 14-year-old groups but low in the 15-year-old group (-7.3%). Concerning the nutritional state, energy, calcium (Ca), and iron intakes were insufficient in every age group. BMD relative to the standard BMD value for Japanese (standard value was regarded as 0%) was evaluated according to the ingestion frequency of Ca-rich foods. The relative BMD value (%) increased with the ingestion frequency of Ca-rich foods. These results suggest that maintenance of an appropriate physique and adequate intake of nutrients such as Ca are important for bone growth during adolescence. Active promotion of educational guidance mainly on the effects of diet on bone health in adolescents in necessary.     

Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus

Cytokines such as interleukin-1 beta (IL-1 beta) are released in the nervous system following inflammation or infection. Recently, IL-1 beta was shown to enhance synaptic inhibitory mechanisms. We therefore investigated the effect of IL-1 beta superfusion on long-term potentiation (LTP), the cellular model of memory and learning, evoked in the CA1 region by tetanic stimulation of the stratum radiatum in the rat hippocampal slice. IL-1 beta (150 pM-1.5 nM) superfused 10 min before tetanic stimulation significantly reduced LTP of the slope of the population excitatory postsynaptic potential (pEPSP) and the population spike (PS) amplitude in CA1 in a concentration-dependent manner. IL-1 beta (1.5 nM) applied for 10 min 1 h before tetanus significantly inhibited LTP of the PS amplitude and pEPSP slope and reduced pEPSP and PS values before tetanus as well, although the PS returned to control values before tetanus. Heat-inactivated IL-1 beta had no effect on pre-tetanus pEPSP or PS values or the induction of LTP. These data demonstrate that IL-1 beta modulates synaptic potentials and reduces LTP. These findings have important implications for the role of IL-1 beta in neuronal disorders following infection, perhaps best exemplified by HIV-1-associated dementia.     

Neuroactive steroids induce GABA(A) receptor-mediated depolarizing postsynaptic potentials in hippocampal CA1 pyramidal cells of the rat

Intracellular recordings were performed in area CA1 pyramidal cells of rat hippocampal slices to determine the effects of certain steroids on inhibitory postsynaptic potentials/currents (IPSP/Cs) mediated by GABA(A) receptors. Following application of the steroids 5alpha-pregnan-3alpha,21-diol-20-one (5alpha-THDOC), alphaxalone and 5beta-pregnan-3alpha-ol-20-one (pregnanolone) hyperpolarizing PSPs developed into biphasic responses consisting of an early hyperpolarizing and a late depolarizing PSP sequence. Steroid-induced depolarizing PSPs could be elicited in the presence of antagonists to non-NMDA, NMDA, and GABA(B) receptors, indicating that these receptor types do not contribute significantly to the initiation of these responses. Depolarizing PSPs were completely blocked by both GABA(A) receptor antagonists bicuculline and t-butylbicyclophosphorothionat (TBPS) providing evidence for their mediation by GABA(A) receptors. The reversal potential of steroid-induced late inward PSCs, measured in single-electrode voltage clamp, was -29.9+/-5.3 mV, whereas the early outward current, which corresponded to the early hyperpolarizing component of PSPs, reversed at -68.2+/-1.5 mV. Depolarizing PSPs and late inward PSCs were sensitive to reduction of extracellular [HCO3-] and block of carbonic anhydrase by application of acetazolamide. The results suggest that certain neuroactive steroids can induce GABA(A) receptor-mediated depolarizing PSPs, which are dependent on HCO3-.     

Transient neurophysiological changes in CA3 neurons and dentate granule cells after severe forebrain ischemia in vivo

Transient neurophysiological changes in CA3 neurons and dentate granule cells after severe forebrain ischemia in vivo. J. Neurophysiol. 80: 2860-2869, 1998. The spontaneous activities, evoked synaptic responses, and membrane properties of CA3 pyramidal neurons and dentate granule cells in rat hippocampus were compared before ischemia and 相似文献   

Noradrenergic regulation of synaptic plasticity in the hippocampal CA1 region

The F9 murine embryonal carcinoma cell line represents a well-established system for the study of retinoid signaling in vivo. We have investigated the functional specificity of different retinoid X receptor (RXR)-retinoic acid (RA) receptor (RAR) isotype pairs for the control of expression of endogenous RA-responsive genes, by using wild-type (WT), RXR alpha(-/-), RAR alpha(-/-), RAR gamma(-/-), RXR alpha(-/-)-RAR alpha(-/-), and RXR alpha(-/-)-RAR gamma(-/-) F9 cells, as well as panRXR and RAR isotype (alpha, beta, and gamma)-selective retinoids. We show that in these cells the control of expression of different sets of RA-responsive genes is preferentially mediated by distinct RXR-RAR isotype combinations. Our data support the conclusion that RXR-RAR heterodimers are the functional units transducing the retinoid signal and indicate in addition that these heterodimers exert both specific and redundant functions on the expression of particular sets of RA-responsive genes. We also show that the presence of a given receptor isotype can hinder the activity of another isotype and therefore that functional redundancy between retinoid receptor isotypes can be artifactually generated by gene knockouts.     

Interleukin-1beta expression after inhibition of protein phosphatases in endotoxin-tolerant cells

BACKGROUND: There are cogent reasons why public health specialists should take an active interest in and measure the psychological health and well-being of populations. The literature was searched and reviewed with the aim of evaluating survey instruments that would enable public health specialists to measure the psychological health and well-being of populations. METHODS: The search and review were restricted to instruments that were applicable to adults of working age, and that did not focus on psychotic disorder or organic brain disorder. An attempt was also made to identify instruments that were designed to measure some form of positive well-being and could be applied in population-based surveys. Detailed evaluation was then carried out of two or three instruments that appeared representative of a particular field or approach. RESULTS: The literature search revealed three major fields of research, 'Psychiatric Epidemiology', 'Stress Studies' and 'Subjective Well-being'. Accordingly, the results of the review are presented under these three headings. Results pertaining to commonly used survey instruments in the field of 'Psychiatric Epidemiology' are presented. (Those on 'Stress Studies' and 'Subjective Well-being' are presented in Part 2 of this study.) CONCLUSIONS: Although some questionnaires in the field of 'Psychiatric Epidemiology', such as the General Health Questionnaire and the HAD Scale, offer a valid and convenient means of measuring degrees of neurotic disorder in a population, they do not measure any form of positive well-being. In Part 2, methods of measurement from the other two fields are reviewed and overall conclusions are drawn about the options available to public health specialists.     

Differential subcellular regulation of NMDAR1 protein and mRNA in dendrites of dentate gyrus granule cells after perforant path transection

Unilateral transection of the excitatory perforant path results in the acute deafferentation of a segregated zone on the distal dendrites of hippocampal dentate gyrus granule cells (i.e., outer molecular layer), followed by sprouting, reactive synaptogenesis, and a return of physiological and behavioral function. To investigate cellular mechanisms underlying NMDA receptor plasticity in response to such extensive synaptic reorganization, we quantitatively evaluated changes in intensity levels of NMDAR1 immunofluorescence and NMDAR1 mRNA hybridization within subcellular compartments of dentate gyrus granule cells 2, 5, and 9 d after perforant path lesions. There were no significant changes in either measure at 2 d postlesion. However, at 5 and 9 d postlesion, during the period of axonal sprouting and synaptogenesis, there was an increase in NMDAR1 immunolabeling that was restricted to the dendritic segments of the denervated outer molecular layer and the granule cell somata. In contrast, NMDAR1 mRNA levels at 5 and 9 d postlesion increased throughout the full extent of the molecular layer, including both denervated and nondenervated segments of granule cell dendrites. These findings reveal that NMDAR1 mRNA is one of a limited population of mRNAs that is transported into dendrites and further suggest that in response to terminal proliferation and sprouting, increased mRNA transport occurs throughout the full dendritic extent, whereas increased local protein synthesis is restricted to denervated regions of the dendrites whose afferent activity is perturbed. These results begin to elucidate the dynamic postsynaptic subcellular regulation of receptor subunits associated with synaptic plasticity after denervation.     

NMDA receptor-dependent and metabotropic glutamate receptor-dependent forms of long-term depression coexist in CA1 hippocampal pyramidal cells

The development and maturation of the endolymphatic sac (ES) and duct (ED) were studied in the newt Cynops pyrrhogaster. The ES first appears as an oval capsule at the dorsal-medial tip of the otic vesicle at stage 39, about 11 days after oviposition. The ES consists of polymorphous epithelial cells with a minimum of cytoplasm. The intercellular space (IS) between the epithelial cells is narrow and has a smooth surface. At stage 44, the size of the ES increases as many vacuoles in the IS become filled. At stage 46, 18 days after oviposition, the ES elongates markedly and a slit-like lumen is found in the ES. The epithelium contains a few cell organelles which are scattered in the cytoplasm. The vacuoles in the IS are fused, which expands the IS. Two days later (stage 48), floccular material (endolymph) is present in the expanded lumen. The IS dilates and has a wide and irregular appearance. At stage 50, approximately 26 days after oviposition, the ES extends and expands significantly and crystals (otoconia) can now be seen in the widened lumen of the ES. The cytoplasm of the cuboidal epithelial cells contains an abundance of vesicles surrounded by ribosomes and Golgi complexes. Intercellular digitations are formed in the expanded IS. At stage 54, the ES forms a large bellow-like pouch. Numerous otoconia accumulate in the lumen. Free floating cells and cell debris can be seen in the lumen at this stage. The epithelial cells contain numerous cytoplasmic organelles which are evenly distributed in the cytoplasm. Granules are found in the apical and lateral cytoplasm. The IS is loose and displays a labyrinthine appearance. The primitive ED first appears as a connection between the ES and the saccule but no lumen is present inside at stage 39. At stage 46, a narrow lumen is formed in the ED, which corresponds to the formation of the ES lumen. At stage 50, as the ED extends, floccular material is seen in the lumen. At stage 54, the ED bears numerous microvilli on its luminal surface. Otoconia and endolymph are present in the ED. Tight junctions between the epithelial cells are formed at stage 46. A fully developed intercellular junctional complex is produced at stage 54. Based on the development of the ES and ED, the maturation of function of the ES and ED are discussed.