RESUMEN
Synaptosomes treated with radioactive gamma-aminobutyric acid can be stimulated to release this substance. The release is maximal within 40 seconds after stimulation and is dependent on calcium. Magnesium and manganese ions, known to block stimulus-secretion coupling processes, depress calcium-dependent release. This release is specific to synaptosomes because microsomal or myelin fractions do not release accumulated gamma-aminobutyric acid. The data illustrate a simple in vitro system suitable for analysis of secretion of gamma-aminobutyric acid in brain and in addition describe several new aspects of uptake and secretion of this compound at brain nerve endings.
Asunto(s)
Aminobutiratos/metabolismo , Encéfalo/metabolismo , Terminaciones Nerviosas/metabolismo , Vesículas Sinápticas/metabolismo , Animales , Calcio/antagonistas & inhibidores , Calcio/farmacología , Isótopos de Carbono , Técnicas In Vitro , Magnesio/farmacología , Manganeso/farmacología , Ratas , Estimulación Química , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismoRESUMEN
Long-term potentiation (LTP) in the rat dentate gyrus is a multifaceted phenomenon, including synaptic potentiation; simultaneous synaptic depression at neighboring, unconditioned synapses; and a change in the amount of cell firing produced by a specified amount of synaptic current (see Levy and Desmond: In G. Buzsaki and C. Vanderwolf (eds): Electrical Activity of The Archicortex. Budapest: Akademiai Kiado, pp. 359-373, '85b). This study presents long-term anatomical modifications that seem related to excitatory synaptic modification. These anatomical alterations appear early and persist for at least 60 minutes following conditioning stimulation. Each animal received test pulse stimulation delivered alternately to the angular bundles before and after brief, unilateral high-frequency conditioning stimulation that is typical of many LTP paradigms. Anatomical preparation followed standard procedures. Double-blind scoring procedures quantified the number of asymmetric synapses in the dentate molecular layer. These counts were converted to the number of synapses per unit volume using stereological corrections that combined geometrically derived theory and modest serial sectioning. Multivariate analysis of variance evaluated the statistical significance of changes in synapse density. Across all three groups of animals, conditioning stimulation does not significantly change the density of synaptic contacts across the entire molecular layer. There is a trend for a decreased density of synaptic contacts in the middle molecular layer, the region activated by the conditioning stimulation. Here the density of concave spine profiles increases significantly in all three groups of animals with conditioning stimulation. This increase accompanies significant decreases in the density of nonconcave, simple and ellipsoid, spine profiles. No significant changes in the density of shaft synapses occur with LTP-inducing conditioning stimulation. These data suggest that the concave spine profiles are a correlate of LTP-inducing stimulation and may be the potentiated synapses. We hypothesize that with synaptic potentiation there occurs an interconversion of spine synapses such that some nonconcave spine profiles become concave spine profiles. Such an interconversion apparently begins shortly after the conditioning stimulation and persists for at least 60 minutes.
Asunto(s)
Hipocampo/fisiología , Plasticidad Neuronal , Transmisión Sináptica , Animales , Hipocampo/ultraestructura , Masculino , Microscopía Electrónica , Ratas , Ratas Endogámicas , Sinapsis/fisiología , Sinapsis/ultraestructuraRESUMEN
The present study documents alterations in the size of the postsynaptic density (PSD) of synapses formed by entorhinal afferents with granule cell dendritic spines with long-term potentiation (LTP). These changes appear early and persist for at least 60 minutes after LTP-inducing conditioning stimulation. Each animal received test and conditioning stimulation typical of LTP paradigms. Electron microscopic preparation of the dentate gyri from each animal followed conventional procedures. PSD trace lengths of identified asymmetric synaptic profiles were measured. The total PSD length for four categories of synaptic profiles was determined for each third of the molecular layer. PSD surface area per unit volume of tissue (SV) was then computed from these data. Statistical analysis of the SV data used multivariate analysis of variance. PSD surface area per synapse was also estimated. Total PSD surface area per unit volume does not change significantly throughout the entire molecular layer with LTP-inducing conditioning stimulation. However, in the activated portion of the molecular layer, total PSD surface area per unit volume tends to increase with conditioning stimulation. In the middle third of the molecular layer, total PSD surface area per unit volume associated with the concave spine profiles increases significantly while there is a statistically significant decrease in total PSD SV associated with the nonconcave spine profiles. The PSD surface area per synapse also increases markedly. Since it seems that there is an interconversion of spine synapses from nonconcave to concave with LTP (Desmond and Levy: J. Comp. Neurol. In press, '86a), these data suggest that potentiated synapses have larger responses because, in part, they have larger neurotransmitter receptive regions.
Asunto(s)
Hipocampo/fisiología , Plasticidad Neuronal , Transmisión Sináptica , Animales , Dendritas/ultraestructura , Hipocampo/ultraestructura , Masculino , Microscopía Electrónica , Ratas , Ratas Endogámicas , Sinapsis/ultraestructuraRESUMEN
The granule cell dendritic fields of the adult rat dentate gyrus were analyzed quantitatively using a probabilistic method developed to correct dendritic length and segment number for dendrites cut during sectioning. Golgi-impregnated, linearized hippocampi were sectioned serially in one of the three hippocampal planes. Three dendritic field parameters were quantified from camera lucida drawings of these dendritic fields: dendritic field spread, dendritic length, and the branching and termination patterns of dendritic segments. Granule cell dendritic fields resembled cones, their maximal extent occurring in the distal third of the molecular layer. The ratio of transverse to longitudinal dendritic field spread was greater than 1:1 for the dorsal leaf and crest regions, but close to or less than 1:1 for the ventral leaf. The probabilities of segment branching and termination were highly similar for transversely and longitudinally sectioned tissue. The probability of branching varied among dendritic orders and across the molecular layer for the same order. The probability of termination did not vary greatly across orders. Most nonbranching segments terminated adjacent to the hippocampal fissure. On the average, a granule cell had 2.23 first-order dendrites that branched into a dendritic field containing seventh-order dendrites. Total dendritic length, corrected for cut dendrites and projection errors, averaged 3,662 +/- 88 microns. The somatic layer and proximal third of the molecular layer contained approximately 35% of this total length. The remainder, ca. 60%, was restricted to the distal two-thirds of the molecular layer, the predominant termination zone of perforant path axons. These data provide a quantitative characterization of the rat granule cell dendritic fields. Implementation of the probabilistic correction method overcomes methodological problems common to quantitative Golgi studies. These data permit a more precise relationship to be drawn between dendritic architecture and granule cell physiology.
Asunto(s)
Dendritas/ultraestructura , Granulocitos/ultraestructura , Hipocampo/citología , Probabilidad/métodos , Ratas/anatomía & histología , Animales , Hipocampo/ultraestructura , Masculino , Ratas EndogámicasRESUMEN
A quantitative examination of granule cell dendritic caliber and knowledge of dendritic lengths allows assessment of the distribution of dendritic membrane and the 3/2 power relationship at branch points. This paper presents caliber data of Golgi-impregnated rat dentate gyrus. We used camera lucida drawings of the dendritic trees of 15 dorsal leaf and 15 ventral leaf granule cells to quantify mean dendritic caliber, dendritic taper, the 3/2 power relationship of parent and sibling dendritic diameters at branch points, and surface area. First-order dendrites vary substantially in diameter. However, the mean caliber of all other dendrites is uniform across the proximal two-thirds of the molecular layer for the dorsal and ventral leaves. The average diameter here is 1 micron. More distally, only mean ventral leaf dendritic caliber declines. Granule cell dendritic taper is due primarily to caliber decreases at branch points and not to a gradual decline in diameter across the length of a dendritic segment. Comparing the parent segment diameter raised to the 3/2 power with the sum of the 3/2 powers of the two sibling segment diameters reveals, for the dendritic tree located within the distal two-thirds of the molecular layer, the desired 3/2 power relationship for the dorsal and ventral leaves. More proximally, where first-, second-, and third-order dendrites branch sequentially across a 60-100-micron extent, a 3/2 power relationship is not obtained. For the average dorsal leaf granule cell, dendritic surface area (without spines) is 11,984 micron2. The ratio of dendritic to somatic surface area is 28:1. Discussion of these data includes their implications for electrotonic modeling of the dentate granule cell.
Asunto(s)
Hipocampo/citología , Animales , Biometría , Dendritas/ultraestructura , Masculino , Ratas , Ratas EndogámicasRESUMEN
Hippocampal functions, e.g. synaptic plasticity and hippocampal-dependent behavior, are influenced by the circulating levels of ovarian steroids in adult, female rats. The mechanisms underlying this estradiol-dependent modulation, however, are poorly understood. One possibility is that estradiol alters N-methyl-D-aspartate (NMDA)-receptor functioning in the hippocampus. Here, using the in vitro hippocampal slice preparation, we evaluate estradiol-dependent changes in the NMDA receptor- and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated components of excitatory postsynaptic potentials (EPSPs) evoked in CA1 by Schaffer collateral test stimulation. Using established experimental conditions [J Neurosci 17 (1997) 1848], we replicate the observation that estradiol pretreatment of ovariectomized rats increases a pharmacologically isolated NMDA receptor-mediated EPSP evoked by Schaffer collateral stimulation. However, using different conditions that optimize study of this evoked response, the estradiol-dependent increase in the monosynaptic NMDA receptor-mediated EPSP is eliminated. Low-intensity test stimulation of the Schaffer collaterals in this optimized medium reveals a novel, late NMDA receptor-mediated EPSP in CA1 from estradiol-pretreated rats. The mechanism(s) underlying this estradiol-dependent increase in a late, NMDA receptor-mediated EPSP is not known, but enhanced CA1-CA1 excitatory circuitry and glutamate spillover could contribute to this response. We conclude that estradiol pretreatment enhances NMDA receptor function in the female hippocampus by increasing not the monosynaptic, but rather a late NMDA receptor-mediated response. Variations in the magnitude of this late response may well contribute to ovarian steroid-dependent modulation of hippocampal synaptic plasticity.
Asunto(s)
Estradiol/metabolismo , Hipocampo/fisiología , Plasticidad Neuronal/fisiología , Células Piramidales/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Técnicas de Cultivo de Órganos , Ovariectomía , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley , Receptores AMPA/metabolismoRESUMEN
1 Isolated synaptosomal fractions from mouse forebrains were incubated [14C]-gamma-aminobutyric acid ([14C]-GABA). Release of the accumulated label in high potassium solution was measured. 2 The fractional release dependent upon calcium was decreased by raising the concentration of [14C]-GABA during labeling but was not affected by altering the time allowed for labelling or the time between labelling and stimulation. 3 These data suggest that extracellular GABA gains rapid access to available intraterminal pools. The relative distribution of the accumulated GABA in differerent pools can be influenced by the concentration of GABA in the incubation medium but, once (stored", there is no net redistribution of accumulated GABA in the absence of stimulation.
Asunto(s)
Encéfalo/metabolismo , Neurotransmisores/metabolismo , Animales , Encéfalo/ultraestructura , Calcio/farmacología , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Técnicas In Vitro , Cinética , Masculino , Norepinefrina/metabolismo , Ratas , Sinaptosomas/metabolismo , Factores de Tiempo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The hippocampus is generally thought to play a modulating role in the timing of conditioned responses in classical trace conditioning. One hypothesis is that the hippocampus stores a memory trace of the conditioned stimulus (CS) during the stimulus-free period. Cellular recordings, however, do not show any obvious CS storage. This article examines this issue by using a biologically plausible model of the CA3 region of the hippocampus. Simulations of the model reproduce both behavioral and physiological experimental data. On the basis of neural codes that develop in the model, the authors hypothesize that the hippocampus functions as a time-indexed encoding device for the CS and not as a CS storage buffer. Specifically, the CS initiates a sequence of neural activity during the trace interval that only indirectly represents the CS. The model yields 2 predictions: Some cells will increase in activity only during the trace interval, and some unconditioned stimulus (US)-coding cells will shift in time and fire before US onset.
Asunto(s)
Condicionamiento Clásico , Hipocampo/fisiología , Memoria/fisiología , Modelos Biológicos , Animales , Ratas , Reproducibilidad de los ResultadosRESUMEN
The number of synapses in the adult, female hippocampal CA1 region fluctuates naturally across the estrous cycle in an ovarian steroid-dependent manner. This phasic variation in synapse number occurs without identifiable degenerating synapses. Ultrastructural correlates of the dynamic aspect of this synapse loss and synapse formation thus remain undescribed. During early development, one hallmark of synaptogenesis is the presence of free postsynaptic densities (PSDs). Here we report that the incidence of free PSDs in CA1 fluctuates across the rat estrous cycle. The number of free PSDs is greatest on the afternoon of proestrus and is significantly decreased on the afternoon of estrus, 24 h later. We hypothesize that these free PSDs reflect synapse turnover in the adult CA1 region.
Asunto(s)
Hipocampo/ultraestructura , Sinapsis/ultraestructura , Animales , Astrocitos/fisiología , Axones/fisiología , Recuento de Células , Estro/fisiología , Femenino , Hipocampo/citología , Neurópilo/citología , Neurópilo/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
This report analyzes long term potentiation (LTP) and associative interactions between synapses of the ipsilateral and crossed entorhinal cortical (EC) pathways to the dentate gyrus (DG). In the anesthetized rat, conditioning stimulation to one EC-DG pathway reliably elicits LTP at the ipsilateral synapses, while the synapses of the collateral, crossed pathway to the contralateral DG do not exhibit LTP. Furthermore, in the DG ipsilateral to the conditioning stimulation the convergent crossed pathway from the contralateral side, which had not been itself conditioned, failed to exhibit heterosynaptic LTP. These results are consistent with a specific 'synaptic' localization of the changes responsible for LTP, and suggest that some critical number of synapses must be activated in order to observe LTP. While the crossed EC-DG projection never exhibited LTP when conditioned alone, the crossed input could be potentiated under certain circumstances. Specifically, paired conditioning of ipsi- and contralateral inputs by nearly simultaneous conditioning stimulation of the EC bilaterally results in LTP in the crossed system. Furthermore, this associatively induced LTP of the crossed system can be reversed by subsequent conditioning of the ipsilateral system alone. Successive potentiating and depotentiating sequences are possible using paired and non-paired stimulation procedures even after lesions which prevent neural loops through the EC. The results are interpreted as evidence for a 'Hebb' type synapse which has the capability for erasure. This synaptic type is not appropriate for classical conditioning without appendant circuitry, but is suited for other forms of associative learning.
Asunto(s)
Aprendizaje por Asociación/fisiología , Hipocampo/fisiología , Aprendizaje/fisiología , Memoria/fisiología , Recuerdo Mental/fisiología , Sinapsis/fisiología , Animales , Condicionamiento Psicológico/fisiología , Dominancia Cerebral/fisiología , Vías Eferentes/fisiología , Estimulación Eléctrica , Potenciales Evocados , Sistema Límbico/fisiología , Masculino , RatasRESUMEN
Using intact, urethane-anesthetized albino rats, we examine long-term depression (LTD) of the ipsilateral medial entorhinal cortical (MEC) response in the dentate gyrus (DG) that is induced by conditioning of the ipsilateral lateral entorhinal cortex (LEC). Although the LEC-DG response potentiates, conditioning the LEC induces little or no LTD of the MEC-DG response. However, bicuculline methiodide, and the correlated presence of population spikes, enable the LEC input to induce LTD of the MEC-DG response. This result suggests that inhibition can control the selectivity of translaminar interactions.
Asunto(s)
Bicuculina/farmacología , Hipocampo/fisiología , Potenciación a Largo Plazo/efectos de los fármacos , Animales , Estimulación Eléctrica , Potenciales Evocados/efectos de los fármacos , Lateralidad Funcional , Hipocampo/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
In many regions NMDA receptor activation is required for the synaptic induction of long-term potentiation (LTP). This role for NMDA receptors is controversial at the synapses formed between the cells of the lateral entorhinal cortex (LEC) and the dentate gyrus (DG). Using anesthetized rats, the present study shows that ketamine reversibly blocks the induction of LTP at the LEC-DG synapses, thus favoring a role for NMDA receptors in the induction of LTP there. Ketamine also reversibly blocks the induction of the small translaminar depression of the medial EC response or of the LEC response by conditioning the other system while the test system is inactive.
Asunto(s)
Potenciales Evocados/efectos de los fármacos , Hipocampo/fisiología , Ketamina/farmacología , Sinapsis/efectos de los fármacos , Animales , Hipocampo/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/fisiología , Sinapsis/fisiología , Factores de TiempoRESUMEN
The present study continues our attempt to understand the ultrastructural changes that accompany and may underlie long-term potentiation (LTP). This report describes changes with LTP in the surface area of the pre- and postsynaptic membrane apposition at the synapses formed by entorhinal cortical (EC) axons with granule cell dendritic spines of the dentate gyrus (DG). The electrophysiology and electron microscopy of the DGs from each animal followed conventional procedures. The trace length of the pre- and postsynaptic apposition was measured for identified asymmetric synapses in the dentate molecular layer. The total apposed membrane surface area per unit volume (Sv) was then computed for 4 categories of synaptic profiles for each third of the molecular layer. Statistical analysis of the Sv data used multivariate analyses of variance. Across the entire molecular layer, total apposed Sv does not change significantly with LTP. However, in the activated portion of the molecular layer, total apposed Sv increases significantly, reflecting a significant increase in the apposed Sv for the concave spine profiles there. For these spine profiles, the increased apposed Sv is due to the increased membrane area both at the postsynaptic density and beyond. The average apposed surface area per individual synapse also increases markedly with LTP. The present data support the hypothesis of coordinated pre- and postsynaptic anatomical changes with LTP in the EC-DG system.
Asunto(s)
Hipocampo/fisiología , Sinapsis/fisiología , Animales , Estimulación Eléctrica , Hipocampo/ultraestructura , Microscopía Electrónica , Ratas , Sinapsis/clasificación , Sinapsis/ultraestructuraRESUMEN
Brief high-frequency trains delivered to the monosynaptic entorhinal cortical input to the dentate gyrus result in both increases and decreases of synaptic strength as a function of whether a particular afferent is active during conditioning (associative potentiation/depression). The present report concerns the effect of such brief, high-frequency conditioning trains upon the asymmetric synapses of the rat dentate gyrus molecular layer. Only those animals whose responses increased at least 50% following conditioning stimulation were included in the study. Additional animals were used for one-dimensional current source density analyses to localize the activated synaptic region. Double blind scoring procedures were used to classify and quantify electron micrographic data. Asymmetric synapses were scored as a function of their position in the molecular layer, spine head size and shape, and postsynaptic density length. All data were treated as inherently matched comparisons between the conditioned and control sides of each animal. The number of large, concave spine synapses with large postsynaptic densities significantly increases in the central zone of synaptic activation. Bordering this zone are regions with increases in synaptic number following conditioning, primarily due to an increased number of small spine synapses. The increased number of large, concave spine synapses in the central zone is postulated to mediate associative potentiation. The many small spine heads just adjacent to the zone of strongest synaptic activation may reflect synaptic depression evoked at synapses inactive during conditioning.
Asunto(s)
Asociación , Hipocampo/ultraestructura , Animales , Mapeo Encefálico , Electrofisiología , Hipocampo/fisiología , Masculino , Memoria/fisiología , Microscopía Electrónica , Modelos Neurológicos , Ratas , Ratas Endogámicas , Sinapsis/fisiología , Sinapsis/ultraestructuraRESUMEN
This paper reports a study of long-term potentiation (LTP) of perforant path synapses in CA1. Using rat hippocampal slices with CA3 and the dentate gyrus removed, stimulation of the perforant path evoked a population excitatory postsynaptic potential (pEPSP) that was negative-going in s. lacunosum-moleculare of CA1. High-frequency conditioning stimulation of the perforant pathway induced LTP of the perforant path pEPSP in slices disinhibited by the GABAA receptor antagonist bicuculline methiodide (20 microM). Conditioning of the perforant pathway in normal medium, however, failed to induce LTP. Potentiation of the perforant path pEPSP in the presence of bicuculline lasted at least 1 h, was specific to the tetanized pathway, and based on a threshold property, appeared associative in nature.
Asunto(s)
Hipocampo/fisiología , Sinapsis/fisiología , Animales , Bicuculina/farmacología , Condicionamiento Psicológico , Estimulación Eléctrica , Electrofisiología , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
The crossed temporodentate pathway from the entorhinal cortex of one hemisphere which proliferates in response to a contralateral entorhinal lesion in adult rats was analyzed for its ability to exhibit long term potentiation of synaptic efficacy similar to that which occurs in the normal ipsilateral temporodentate pathway. It was found that while the small synaptic response evoked by contralateral entorhinal cortical stimulation in normal rats does not undergo long term potentiation, after unilateral entorhinal lesions and proliferation of the crossed temporodentate pathway, the crossed pathway acquires a capacity for potentiation of synaptic action which qualitatively resembles that of the normal ipsilateral temporodentate circuit. However, despite the potentiation of synaptic drive, no long term enhancement of cell discharge was observed in the re-innervated dentate gyrus even through potentiation of this parameter was very prominent in the ipsilateral pathway. Mechanisms are discussed by which a previously non-potentiating pathway may acquire, as a consequence of lesion-induced sprouting, an ability to undergo long term potentiation of synaptic efficacy in a fasion similar to the ablated pathway. Reasons for the failure to observe potentiation of cell firing are also considered.
Asunto(s)
Corteza Cerebral/fisiología , Hipocampo/fisiología , Acetilcolinesterasa/análisis , Animales , Vías Eferentes/fisiología , Estimulación Eléctrica , Potenciales Evocados , Masculino , Ratas , Sinapsis/fisiologíaRESUMEN
The induction of long-term potentiation (LTP) in the dentate gyrus (DG) leads to a change in the firing characteristics of the dentate granule cells. This phenomenon, termed EPSP/spike dissociation, is seen in field potential studies as a shift to the left of the E-S curve, in which population spike amplitude is plotted against pEPSP slope at various stimulus intensities. It has been suggested that EPSP/spike dissociation reflects a decrease in feed-forward inhibition. To test this hypothesis, we blocked GABA-A neurotransmission in a circumscribed area of the DG in urethane-anaesthetized rats by inserting a micropipette filled with 8 mM bibuculline methiodide in saline. We then recorded E-S curves from 9 such electrodes and from 8 control electrodes before and after inducing LTP in the perforant path. Bicuculline prevented the LTP-associated leftward shift of the E-S curves. Instead, the E-S curve showed a consistent shift to the right at the bicuculline sites after LTP, reflecting potentiation of the pEPSP without corresponding increases in the population spike amplitude. The results indicate that the EPSP/spike relationship is controlled largely by GABAergic input, and that potentiation of the population spike in the DG depends largely on a change in the EPSP/spike relationship.
Asunto(s)
Potenciales Evocados/fisiología , Hipocampo/fisiología , Ácido gamma-Aminobutírico/fisiología , Potenciales de Acción/fisiología , Animales , Bicuculina/análogos & derivados , Bicuculina/farmacología , Masculino , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
The present study quantified ribosomes, as an ultrastructural marker of neuronal protein synthesis, following long-term potentiation (LTP) in the hippocampal CA1 region in vitro. Sixty min after LTP-inducing, high-frequency stimulation of the perforant path, the total number of ribosomes, the number of polysomes, and the number of membrane-bound ribosomes increased significantly. These increases are a postsynaptic morphological correlate consistent with enhanced protein synthesis following the induction of LTP in the perforant path-CA1 system.
Asunto(s)
Hipocampo/fisiología , Tractos Piramidales/fisiología , Ribosomas/fisiología , Ribosomas/ultraestructura , Sinapsis/fisiología , Animales , Estimulación Eléctrica , Hipocampo/ultraestructura , Técnicas In Vitro , Masculino , Microscopía Electrónica , Polirribosomas/fisiología , Polirribosomas/ultraestructura , Tractos Piramidales/ultraestructura , Ratas , Ratas Sprague-Dawley , Sinapsis/ultraestructuraRESUMEN
Long-term potentiation (LTP) can be readily elicited in a number of hippocampal pathways, but has not been seen in the dentate commissural pathway. The dentate commissural pathway is similar to the commissural/Schaffer collateral projection to CA1 except that it produces powerful inhibition that occurs nearly concurrently with the excitation. The present study evaluates whether this inhibition prevents the pathway from expressing LTP. Acute neurophysiological experiments were carried out in urethane anesthetized rats. To locally block inhibition in the dentate gyrus, a recording micropipette filled with 8 mM bicuculline was positioned in the dentate gyrus. A control saline-filled micropipette was positioned nearby. The commissural pathway was activated by stimulating electrodes in the contralateral CA3/CA4 region. Brief high-frequency stimulation of the commissural pathway reliably elicited LTP at the bicuculline electrode but not at the control electrode. This LTP required a threshold level of stimulation for its initiation, suggesting that like most other examples of LTP, the LTP in the commissural system depended upon activation of a voltage-dependent receptor. The high-frequency stimuli used to induce LTP produced an extracellular negativity at the bicuculline electrode that was not present at the control electrode. This negative potential was selectively blocked by ketamine and MK801, suggesting that the negative potential reflects N-methyl-D-aspartate (NMDA) receptor activation. Taken together, these results suggest that LTP is not normally expressed by the dentate commissural pathway because the simultaneous inhibition prevents the depolarization-related relief of Mg2+ blockade of the NMDA receptor.
Asunto(s)
Bicuculina/farmacología , Hipocampo/fisiología , Inhibición Neural/efectos de los fármacos , Animales , Estimulación Eléctrica , Hipocampo/efectos de los fármacos , Masculino , Ratas , Ratas EndogámicasRESUMEN
The number of dendritic spine synapses in the hippocampal CA1 stratum radiatum fluctuates across the rat estrous cycle, being high on proestrus and low on estrus [20]. We hypothesized that the volume occupied by astrocytic processes changes in a complementary manner. The volume fraction of astrocytic processes was determined stereologically in CA1 s. radiatum and s. lacunosum-moleculare of cycling female rats. Consistent with our hypothesis, the volume fraction was significantly lower on the afternoon of proestrus than on the afternoon of estrus in both laminae.