[Esterases in the hippocampus of Wister rats. 1. Review of the esterase types found in the hippocampus].
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Acetylcholinesterase↗
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Differential expression of NMDA and AMPA receptor subunits in rat dorsal and ventral hippocampus.
Several studies have demonstrated anatomical and functional segregation along the dorsoventral axis of the hippocampus. This study examined the possible differences in the AMPA and NMDA receptor subunit composition and receptor binding parameters between dorsal and ventral hippocampus, since several evidence suggest diversification of NMDA receptor-dependent processes between the two hippocampal poles. Three sets of rat dorsal and ventral hippocampus slices were prepared: 1) transverse slices for examining a) the expression of the AMPA (GluRA, GluRB, GluRC) and NMDA (NR1, NR2A, NR2B) subunits mRNA using in situ hybridization, b) the protein expression of NR2A and NR2B subunits using Western blotting, and c) by using quantitative autoradiography, c(1)) the specific binding of the AMPA receptor agonist [(3)H]AMPA and c(2)) the specific binding of the NMDA receptor antagonist [(3)H]MK-801, 2) longitudinal slices containing only the cornus ammonis 1 (CA1) region for performing [(3)H]MK-801 saturation experiments and 3) transverse slices for electrophysiological measures of NMDA receptor-mediated excitatory postsynaptic potentials. Ventral compared with dorsal hippocampus showed for NMDA receptors: 1) lower levels of mRNA and protein expression for NR2A and NR2B subunits in CA1 with the ratio of NR2A /NR2B differing between the two poles and 2) lower levels of [(3)H]MK-801 binding in the ventral hippocampus, with the lowest value observed in CA1, apparently resulting from a decreased receptor density since the B(max) value was lower in ventral hippocampus. For the AMPA receptors CA1 our results showed in ventral hippocampus compared with dorsal hippocampus: 1) lower levels of mRNA expression for GluRA, GluRB and GluRC subunits, which were more pronounced in CA1 and in dentate gyrus region and 2) lower levels of [(3)H]AMPA binding. Intracellular recordings obtained from pyramidal neurons in CA1 showed longer NMDA receptor-mediated excitatory postsynaptic potentials in ventral hippocampus compared with dorsal hippocampus. In conclusion, the differences in the subunit mRNA and protein expression of NMDA and AMPA receptors as well as the lower density of their binding sites observed in ventral hippocampus compared with dorsal hippocampus suggest that the glutamatergic function differs between the two hippocampal poles. Consistently, the lower value of the ratio NR2A/NR2B seen in the ventral part would imply that the ventral hippocampus NMDA receptor subtype is functionally different than the dorsal hippocampus subtype, as supported by our intracellular recordings. This could be related to the lower ability of ventral hippocampus for long-term synaptic plasticity and to the higher involvement of the NMDA receptors in the epileptiform discharges, observed in ventral hippocampus compared with dorsal hippocampus.
Animals↗
Comparisons of dorsal and ventral hippocampus cornu ammonis region 1 pyramidal neuron activity during trace eye-blink conditioning in the rabbit.
Previous studies demonstrating a critical role of the hippocampus during trace eye-blink conditioning have focused primarily upon the dorsal portion of the structure. However, evidence suggests that a functional differentiation exists along the septotemporal axis of the hippocampus. In the present study, the activity of 2588 single cornu ammonis region 1 pyramidal neurons of the dorsal hippocampus and ventral hippocampus were recorded during trace and pseudo-eye-blink conditioning of the rabbit. Learning-related increases in dorsal hippocampus neuron firing rates were observed immediately prior to behavioral criterion, and increased over the course of training. Activation of dorsal hippocampus neurons during trace conditioning was also greater than that of ventral hippocampus neurons, including during the trace interval, in well-trained animals. An unexpected difference in the patterns of learning-related activity between hemispheres was also observed. Neurons of the dorsal hippocampus ipsilateral and contralateral to the trained eye, exhibiting significant increases in firing rate [rate increasing neurons], demonstrated the greatest magnitude of activation early and late in training, respectively. Rate increasing neurons of the dorsal hippocampus also exhibited a greater diversity of response profiles, with 69% of dorsal hippocampus rate increasing neurons exhibiting significant increases in firing rate during the conditioned stimulus and/or trace intervals, compared with only 8% of ventral hippocampus rate increasing neurons (the remainder of which were significantly responsive during only the unconditioned stimulus and/or post-unconditioned stimulus intervals). Only modest learning-related activation of ventral hippocampus neurons was observed, reflected as an increase in conditioning stimulus-elicited rate increasing neuron response magnitudes over the course of training. No differences in firing rate between dorsal hippocampus and ventral hippocampus neurons during a 1-day pre-training habituation session were observed. Thus, dorsal hippocampus activation is more robust, suggesting a more substantial role for these neurons in the processing of temporal information during trace eye-blink conditioning.
Action Potentials↗
Stimulation of serotonergic neuronal maturation after fetal mesencephalic raphe transplantation into the 5,7-DHT-lesioned hippocampus of the adult rat.
Neurotoxin lesioning of 5-HT fibers selectively induced the homotypic collateral sprouting of spared 5-HT fibers in the hippocampus. We have used this model to investigate the possibility that the neurotoxin-primed hippocampus will enhance the development of transplanted fetal serotonergic neurons in the brain. The neurotoxin 5,7-DHT, when microinjected into the FF, produced a specific and partial depletion of 5-HT in the hippocampus of adult rats. The ability of the 5,7-DHT-primed hippocampus to selectively support the neurochemical maturation of fetal serotonergic cells was tested by assaying the transplanted fetal raphe or LC 1 month after neuronal transplantation. The neurochemical maturation of fetal 5-HT and NE neurons was dramatically different when they were transplanted in the 5,7-DHT-FF-lesioned hippocampus as compared to the normal hippocampus. The transplanted 5-HT neurons had 480% more SHAU of [3H]5-HT and had a 250% greater content of 5-HT in the partially denervated hippocampus than in the normal hippocampus after 1 month. Furthermore, extracts obtained from lesioned hippocampus enhanced the 5-HT content of 5-HT neurons transplanted in the normal hippocampus, to a level similar to that seen in neurons transplanted in the lesioned hippocampus. In contrast, the implanted NE neurons of fetal LC had a lower NE level in the 5-HT partially denervated hippocampus than in normal hippocampus after 1 month in the host site. The growth of the NE transplants was not facilitated by the vacant postsynaptic space produced by the 5,7-DHT lesion. These results suggest that the 5-HT denervation triggered a trophic signal selectively enhancing the development of the 5-HT neurons but not the NE neurons. Our results are consistent with previous studies showing homotypic collateral sprouting in 5,7-DHT-primed hippocampus.
5,7-Dihydroxytryptamine↗
Hippocampal neurotrophin levels after injury: Relationship to the age of the hippocampus at the time of injury.
Aging impairs the competence of the hippocampus for synaptic reorganization after injury. This potentially is due to the inability of the aging hippocampus to up-regulate the critical neurotrophic factors for prolonged periods after injury to levels at which they can stimulate neurite outgrowth and facilitate synaptic reorganization. We hypothesize that the concentrations of neurotrophins in the hippocampus after injury depend on the age at the time of injury. We quantified the concentrations of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) in the hippocampus of young, middle-aged, and aged Fischer 344 rats at 4 days after kainic acid (KA)-induced injury. In comparison with the age-matched intact hippocampus, the KA-lesioned hippocampus exhibited increased levels of BDNF and NGF in all three age groups. In contrast, the NT-3 concentration was unaltered after KA lesion. Notwithstanding similar percentage increases in BDNF after injury, the lesioned middle-aged and aged hippocampus contained 45-52% less BDNF than the lesioned young hippocampus. NGF and NT-3 levels after injury were comparable across the three age groups, however. Furthermore, lower BDNF concentration in the injured aging hippocampus was associated with normal astrocytic response but significantly diminished microglial reaction. Thus, in comparison with the injured young hippocampus, the injured aging hippocampus contains considerably less BDNF but similar levels of NGF and NT-3. Lower BDNF levels in the injured aging hippocampus might underlie the diminished spontaneous healing response observed in the aging hippocampus after injury, particularly in terms of synaptic reorganization and dentate neurogenesis.
Aging↗
Intratelencephalic connections of the hippocampus in pigeons (Columba livia).
Behavioral experiments using ablation of the hippocampus are increasingly being used to address the hypothesis that the avian hippocampus plays a role in memory, as in mammals. However, the morphological basis of the avian hippocampus has been poorly understood. In the present study, the afferent and efferent connections of the hippocampus in the pigeon telencephalon were defined by injections, at various rostrocaudal sites, of neuronal tracers mainly into the triangular part located between its V-shaped layer of densely packed neurons. The major results obtained in the present study were as follows. 1) A topographical organization of the commissural projections was confirmed. These projections had two courses that projected to the contralateral side, one traveling through the fiber wall of the ventromedial telencephalon, which was the main path from neurons in the caudal hippocampus, and the other running down through the septohippocampal junction, which was the main path from neurons in the middle to rostral hippocampus. Both courses passed through the pallial commissure. 2) The hippocampus projected bilaterally to the septum, parahippocampal area (APH), and dorsolateral cortical area (CDL). These projections were also distributed topographically, with contralateral efferents crossing through the pallial commissure. 3) The hippocampus had ipsilateral reciprocal connections with APH, CDL, and the dorsal hyperstriatum. Septal afferents to the ipsilateral hippocampus were very small. 4) Intrinsic connections were found between the triangular part of the hippocampus and the lateral limb of the V-shaped layer of neurons. 5) The hippocampus projected ipsilaterally to the ventral basal ganglia and the fasciculus diagonalis Brocae. In sum, these connections of the hippocampus may form a neuronal circuit for the processing of spatial memory in pigeons.
Animals↗
Denervation of serotonergic fibers in the hippocampus induced a trophic factor which enhances the maturation of transplanted serotonergic neurons but not norepinephrine neurons.
The trophic effects of specific denervation on the growth and survival of fetal serotonergic (5-HT) or norepinephrinergic (NE) neurons grafted into the hippocampus were assessed by means of two transplantation paradigms. In the first, fetal raphe cells (containing 5-HT neurons) were transplanted into the control hippocampus. In the second, the transplantation was performed 2 weeks after the specific removal of 5-HT afferents to the hippocampus with 5,7-dihydroxytryptamine (5,7-DHT). We found that a month after transplantation, the number of 5-HT immunoreactive neurons was not significantly different between the two experimental paradigms. However, transplanted raphe neurons had 400% more 5-HT synaptosomal high-affinity uptake and 380% higher content of 5-HT in the hippocampus with prior 5,7-DHT lesion than in control hippocampus. Furthermore, immunocytochemistry showed that the transplanted 5-HT neurons had denser processes and varicosities in the hippocampus with lesion than in control hippocampus. The somatic area of the neurons with these denser processes and varicosities was 42% larger than that of control group. A greater 5-HT level could be achieved if transplanted neurons in the control hippocampus were treated with the supernatant extracted from the hippocampus with 5,7-DHT lesion. In contrast, the NE level of the implanted fetal locus ceruleus (containing NE neurons) was not significantly higher in the 5-HT denervated hippocampus than in control hippocampus a month after transplantation. These results suggest that 5-HT denervation in the hippocampus induces a trophic substance which promotes the maturation rather than survival of 5-HT neurons but not NE neurons.
5,7-Dihydroxytryptamine↗
Dissociable effects of hippocampus lesions on expression of fear and trace fear conditioning memories in rats.
The role of the hippocampus in memory is commonly investigated by comparing fear conditioning paradigms that differ in their reliance on the hippocampus. For example, the dorsal (septal) portion of the hippocampus is involved in trace, but not delay fear conditioning, two Pavlovian paradigms in which only the relative timing of stimulus presentation is varied. However, a growing literature implicates the ventral (temporal) portion of the hippocampus in the expression of fear, irrespective of prior training. The current experiments evaluated the relative contributions of the dorsal and ventral portions of the hippocampus to trace fear conditioning specifically vs. the expression of conditioned fear in general. Lesions restricted to the dorsal hippocampus blocked acquisition of trace fear conditioning. Larger lesions, also including an adjacent portion of the ventral hippocampus, were required to impair retrieval of trace fear conditioning. Delay fear conditioning was not disrupted in either case. In contrast, lesions that encompassed almost the entire dorsal and ventral hippocampus disrupted expression of both trace and delay fear conditioning. The current data suggest distinct roles in fear conditioning for three regions of the hippocampus: the septal zone is required for acquisition of trace fear conditioning, a larger portion of the hippocampus is critical for memory retrieval, and a region including the temporal zone is required for expression of both trace and delay fear conditioning. These findings are consistent with evidence suggesting the neuroanatomical and functional segregation of the hippocampus into three zones along its septal-temporal axis.
Acoustic Stimulation↗
Long-range temporal correlations in epileptogenic and non-epileptogenic human hippocampus.
Epileptogenic human hippocampus generates spontaneous energy fluctuations with a wide range of amplitude and temporal variation, which are often assumed to be entirely random. However, the temporal dynamics of these fluctuations are poorly understood, and the question of whether they exhibit persistent long-range temporal correlations (LRTC) remains unanswered. In this paper we use detrended fluctuation analysis (DFA) to show that the energy fluctuations in human hippocampus show LRTC with power-law scaling, and that these correlations differ between epileptogenic and non-epileptogenic hippocampus. The analysis shows that the energy fluctuations exhibit slower decay of the correlations in the epileptogenic hippocampus compared with the non-epileptogenic hippocampus. The DFA-derived scaling exponents demonstrate that there are LRTC of energy fluctuations in human hippocampus, and that the temporal persistence of energy fluctuations is characterized by a bias for large (small) energy fluctuations to be followed by large (small) energy fluctuations. Furthermore, we find that in the period of time leading up to seizures there is no change in the scaling exponents that characterize the LRTC of energy fluctuations. The fact that the LRTC of energy fluctuations do not change as seizures approach provides evidence that the local neuronal network dynamics do not change in the period before seizures, and that seizures in mesial temporal lobe epilepsy may be triggered by an influence that is external to the hippocampus. The presence of LRTC with power-law scaling does not imply a specific mechanism, but the finding that temporal correlations decay more slowly in epileptogenic hippocampus provides electrophysiologic evidence that the underlying neuronal dynamics are different within the epileptogenic hippocampus compared with contralateral hippocampus. We briefly discuss possible neurobiological mechanisms for LRTC of the energy fluctuations in hippocampus.
Electroencephalography↗
Differential effects on delayed non-matching-to-position in rats of microinjections of muscarinic receptor antagonist scopolamine or NMDA receptor antagonist MK-801 into the dorsal or ventral extent of the hippocampus.
Glutamatergic NMDA and cholinergic muscarinic receptors are thought to contribute to cognitive processes mediated by the hippocampus. Evidence from lesion studies suggests that, despite cytoarchitectural uniformity within the hippocampus, information processing may not be uniform along the septo-temporal axis. The present study examined whether blockade of NMDA or muscarinic receptors in hippocampal subregions produced regional dissociations in the disruption of performance on an operant, spatial delayed non-matching-to-position (DNMTP) paradigm that also assessed vigilance. Rats were extensively pretrained on DNMTP, then bilaterally cannulated into either the dorsal or ventral hippocampus. Following retraining, scopolamine or MK-801 were administered prior to sessions. MK-801 administered into dorsal hippocampus produced delay-independent deficits in DNMTP delayed choice. Neither scopolamine administered into the dorsal or ventral hippocampus, nor MK-801 administered into the ventral hippocampus, produced significant disruption of DNMTP delayed choice. However, some dissociations were evident in other measures of vigilance. Scopolamine into the dorsal and ventral hippocampus increased errors of omission, scopolamine into the ventral hippocampus decreased sample response accuracy, and MK-801 into the dorsal hippocampus decreased sample response accuracy and increased response bias. These results are consistent with the suggestion that subregions of the hippocampus may be involved in different aspects of information processing and also suggest that the cholinergic inputs to the hippocampus may be functionally independent of NMDA receptor-mediated neurotransmission.
Animals↗
MR measurements of the hippocampus for lateralization of temporal lobe epilepsy: value of measurements of the body vs the whole structure.
OBJECTIVE: Measurements of the volume of the hippocampus have been used preoperatively to determine the side of the hippocampus involved in patients with intractable temporal lobe epilepsy. However, the method used is time consuming and requires special training. The purpose of this study was to determine the validity of using measurements of the volume of the hippocampal body as a substitute for measurements of the volume of the whole hippocampus in patients with temporal lobe epilepsy. SUBJECTS AND METHODS: The study group consisted of 33 patients with intractable temporal lobe epilepsy due to presumed hippocampal sclerosis and 30 control subjects. Of the 33 patients with intractable temporal lobe epilepsy, 30 had hippocampal sclerosis and three had normal findings on pathologic examination of the hippocampus. T2-weighted fast spin-echo images were used to determine hippocampal volumes. Volumes were calculated by summing the sectional areas of the entire hippocampus and of the hippocampal body. Correlation between the volume of the hippocampal body and the volume of the whole hippocampus was determined. The sensitivity and specificity of measurement of the volume of the hippocampal body for lateralizing the foci responsible for seizures in patients with presumed hippocampal sclerosis were compared with those of measurement of the volume of the whole hippocampus. RESULTS: Significant linear relationships were noted between volumes of the hippocampal body and volumes of the whole hippocampus (p < .001). The sensitivity and specificity of measurements of volumes of the hippocampal body were identical to those of measurements of volumes of the whole hippocampus (87% and 100%, respectively). CONCLUSIONS: Our results show that segmental MR measurements of the body of the hippocampus are as accurate as measurements of the whole hippocampus for lateralizing temporal lobe epilepsy before surgery. Because segmental measurements are less time consuming and require less experience to perform, they are considered the procedure of choice.
Adolescent↗
[Effects of hypothyroidism on apoptosis and the expression of Bcl-2 and Bax gene in the neonatal rat hippocampus neurons].
OBJECTIVE: During the critical period of brain development, insufficiency of thyroid hormone results in severe mental retardation and learning deficit. This study was designed to investigate the effects of hypothyroidism on apoptosis and the expression of Bcl-2 and Bax gene in the developing rat hippocampus neurons and to explore the mechanism of brain development regulated by thyroid hormone. METHOD: Hypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at postnatal day 1 (P1), P5, P10 and P15, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free tri-iodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by using chemoluminescence. Hippocampus collected from the control and hypothyroid pups were examined under light and transmissional electron microscopy. Measurement of DNA fragmentation was carried out by agarose gel electrophoresis. The expression of Bcl-2 and Bax protein in the developing rat hippocampus neurons was performed by Western blotting. RESULTS: Significantly lower circulating FT(4) and FT(3) levels confirmed the hypothyroid status of the experimental pups. The shrunken and contracted degenerations increased in hippocampus neurons of hypothyroid pups under light microscopy. Enhanced apoptotic cells were found in hippocampus neurons of hypothyroid pups under transmission electron microscopy, especially at P10 and P15. Extensive DNA fragmentation was seen throughout development in hippocampus of hypothyroid pups, but not in the euthyroid controls except for basal level at P10. The expression of Bcl-2 in the hippocampus neurons of hypothyroid pups was significantly lower than that of euthyroid controls at all stages of development (P1: 1.95 +/- 0.27 vs. 2.59 +/- 0.19, P < 0.05, P5: 1.86 +/- 0.24 vs. 2.47 +/- 0.17, P < 0.05, P10: 1.29 +/- 0.22 vs. 1.86 +/- 0.28, P < 0.05 and P15: 1.21 +/- 0.27 vs. 2.18 +/- 0.17, P < 0.01, respectively). The relative amount of expression varied significantly with age in the control pups. The level of Bcl-2 was high in hippocampus neurons of euthyroid at P1, P5, and decreased significantly at P10, and showed a trend of recovery at P15. Similar age-related variation in the expression of Bcl-2 gene was observed in the hypothyroid group at P1, P5 and P10, but the level was maintained low at P15. The expression of Bax in the hippocampus neurons of hypothyroid pups was significantly higher than that of control pups at all stages of development (P1: 1.69 +/- 0.14 vs. 1.24 +/- 0.23, P < 0.05, P5: 1.78 +/- 0.16 vs. 1.29 +/- 0.17, P < 0.05, P10: 1.92 +/- 0.18 vs. 1.45 +/- 0.14, P < 0.05 and P15: 1.86 +/- 0.14 vs. 1.51 +/- 0.12, P < 0.05, respectively). The ratio of Bcl-2/Bax in hippocampus neurons of hypothyroid pups was lower than that of age-matched controls (P1: 1.16 +/- 0.17 vs. 2.12 +/- 0.35, P < 0.05, P5: 1.05 +/- 0.16 vs. 1.94 +/- 0.36, P < 0.05, P10: 0.68 +/- 0.17 vs. 1.29 +/- 0.16, P < 0.05 and P15: 0.67 +/- 0.19 vs. 1.45 +/- 0.22, P < 0.01, respectively). CONCLUSION: Thyroid hormone significantly prevents apoptosis of hippocampus neurons. Congenital hypothyroidism increases not only the extent but also the duration of apoptosis by down-regulation of the anti-apoptotic gene Bcl-2 and maintaining a high level of the pro-apoptotic gene Bax.
Animals↗
Evidence for high-affinity binding sites for the adenosine A2A receptor agonist [3H] CGS 21680 in the rat hippocampus and cerebral cortex that are different from striatal A2A receptors.
The binding of the adenosine A2A receptor selective agonist 2-[4-(2-p-carboxyethyl)phenylamino] -5'-N-ethylcarboxamidoadenosine (CGS 21680) to the rat hippocampal and cerebral cortical membranes was studied and compared with that to striatal membranes. [3H] CGS 21680, in the concentration range tested (0.2-200 nM), bound to a single site with a Kd of 58 nM and a Bmax of 353 fmol/mg protein in the hippocampus, and with a Kd of 58 nM and a Bmax of 264 fmol/mg protein in the cortex; in the striatum, the single high-affinity [3H] CGS 21680 binding site had a Kd of 17 nM and a Bmax of 419 fmol/mg protein. Both guanylylimidodiphosphate (100 microM) and Na+ (100 mM) reduced the affinity of [3H] CGS 21680 binding in the striatum by half and virtually abolished [3H] CGS 21680 binding in the hippocampus and cortex. The displacement curves of [3H] CGS 21680 binding with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), N6-cyclohexyladenosine (CHA), 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CADO) were biphasic in the hippocampus and cortex as well as in the striatum. The predominant [3H]CGS 21680 binding site in the striatum (80%) had a pharmacological profile compatible with A2A receptors and was also present in the hippocampus and cortex, representing 10-25% of [3H]CGS 21680 binding. The predominant [3H]CGS 21680 binding site in the hippocampus and cortex had a pharmacological profile distinct from A2A receptors: the relative potency order of adenosine antagonists DPCPX, 1,3-dipropyl- 8-¿4-[(2-aminoethyl)amino]carbonylmethyl- oxyphenyl¿ xanthine (XAC), 8-(3-chlorostyryl)caffeine (CSC), and (E)-1,3-dipropyl-8-(3,4-dimethoxystyryl)- methylxanthine (KF 17,837) as displacers of [3H] CGS 21680 (5 nM) binding in the hippocampus and cerebral cortex was DPCPX > XAC >> CSC approximately KF 17,837, and the relative potency order of adenosine agonists CHA, NECA, CADO, 2-[(2-aminoethylamino)carbonylethylphenylethylamino]-5'-N- ethylcarboxamidoadenosine (APEC), and 2-phenylaminoadenosine (CV 1808) was CHA approximately NECA > or = CADO > APEC approximately CV1808 > CGS 21680. In the presence of DPCPX (20 nM), [3H] CGS 21680 (0.2-200 nM) bound to a site (A2A-like) with a Kd of 20 nM and a Bmax of 56fmol/mg protein in the hippocampus and with a Kd of 22 nM and a Bmax of 63fmol/mg protein in the cortex. In the presence of CSC (200 nM), [3H]CGS 21680(0.2-200 nM) bound to a second high-affinity site with a Kd of 97 nM and a Bmax of 255 fmol/mg protein in the hippocampus and with a Kd of 112 nM and a Bmax of 221 fmol/mg protein in the cortex. Two pharmacologically distinct [3H]CGS 21680 binding sites were found in synaptosomal membranes of the hippocampus and cortex and in the striatum, one corresponding to A2A receptors and the other to the second high-affinity [3H]CGS 21680 binding site. In contrast, the pharmacology of [3H]CHA binding was similar in synaptosomal membranes of the three brain areas. The present results establish the existence of at least two high-affinity [3H]CGS 21680 binding sites in the CNS and demonstrate that the [3H]CGS 21680 binding site predominant in the hippocampus and cerebral cortex has different binding characteristics from the classic A2A adenosine receptor, which predominates in the striatum.
2-Chloroadenosine↗
Ontogeny and regional distribution of proenkephalin- and prodynorphin-derived peptides and opioid receptors in rat hippocampus.
Levels of prodynorphin- and proenkephalin-derived peptides were determined in whole hippocampus of prenatal and early postnatal rats and in five regions of the hippocampus of the adult rat. Using autoradiography, opioid receptor subtypes were localized in coronal sections of adult hippocampus. The opioid peptides are present in very low concentrations in prenatal hippocampus, with only dynorphin B and alpha-neo-endorphin being present in significant amounts. The main increase in concentrations of the opioid peptides occur between day 7 and 14 postnatally, when dynorphin A, dynorphin A-(1-8), dynorphin B and alpha-neo-endorphin reach their adult levels. beta-Neo-endorphin and [Met]enkephalyl-Arg-Gly-Leu do not reach their maximal level until later in development. There is a distinct differential distribution of the opioid peptides in the subregions of the hippocampus; the subiculum and CA1 are relatively poor in prodynorphin-derived peptides but do contain significant amounts of [Met]enkephalin and [Leu]enkephalin. Very high concentrations of dynorphin B and alpha-neo-endorphin are present in region CA4. Dynorphin A-(1-8) and [Met]enkephalin have their highest concentrations in the dentate gyrus. There is a 5-fold higher concentration of [Met]enkephalin in the ventral hippocampus compared to the dorsal hippocampus. A similar trend is seen with dynorphin A-(1-8) but not with the other opioid peptides. The most abundant opioid receptor population in the hippocampus is of the mu type and it is densest in and around stratum pyramidale of the region CA3. There are relatively few kappa opioid receptors in the rat hippocampus. These results indicate the presence of at least two independent opioid neuronal systems (enkephalin and dynorphin) in rat hippocampus and the presence of mu-, delta- and kappa-opioid receptor subtypes.
Aging↗
Collateral projections from the median raphe nucleus to the medial septum and hippocampus.
It has previously been shown that the median raphe nucleus (MR) is a source of pronounced projections to the septum and hippocampus. The present study examined collateral projections from MR to the medial septum (MS) and to various regions of the hippocampus. The fluorescent retrograde tracers, Fluororuby and Fluorogold, were injected into the septum and hippocampus, respectively, and the median raphe nucleus was examined for the presence of single- and double-labeled neurons. The dorsal raphe nucleus (DR) was also examined for the presence of single- and double-labeled cells and comparisons were made with the MR. The main findings were: (1) pronounced numbers of retrogradely labeled cells (approximately 50 cells/section) were present in MR with injections in the MS or in various regions of the hippocampus; (2) approximately 8-12% of MR cells were double-labeled following paired injections in the MS-CA1, MS-CA3, and MS-dentate gyrus of the dorsal hippocampus, the lateral MS-dentate gyrus, and the MS-ventral hippocampus; (3) single- and double-labeled cells were intermingled throughout MR and present in greater numbers in the rostral than caudal MR; and (4) significantly more single- and double-labeled cells were present in MR than in DR with all combinations of injections. These findings demonstrate that MR projects strongly to the MS and hippocampus, and that a significant population of MR neurons (8-12%) sends collateral projections to both sites. It is well established that the MR nucleus serves a direct role in the desynchronization of the electroencephalographic (EEG) activity of the hippocampus-or the blockade of the hippocampal theta rhythm. The MR neurons that we have identified with collateral projections to the septum and hippocampus may be critically involved in the modulation/control of the hippocampal EEG. A role for the MR in memory associated functions of the hippocampus is discussed.
Action Potentials↗
Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease.
OBJECTIVES: To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine the powers of the ERC and the hippocampus for discrimination between these groups. METHODS: This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation. RESULTS: Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC. CONCLUSIONS: Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.
Aged↗
Sleep restriction suppresses neurogenesis induced by hippocampus-dependent learning.
Sleep deprivation impairs hippocampal-dependent learning, which, in turn, is associated with increased survival of newborn cells in the hippocampus. We tested whether the deleterious effects of sleep restriction on hippocampus-dependent memory were associated with reduced cell survival in the hippocampus. We show that sleep restriction impaired hippocampus-dependent learning and abolished learning-induced neurogenesis. Animals were trained in a water maze on either a spatial learning (hippocampus-dependent) task or a nonspatial (hippocampus-independent) task for 4 days. Sleep-restricted animals were kept awake for one-half of their rest phase on each of the training days. Consistent with previous reports, animals trained on the hippocampus-dependent task expressed increased survival of newborn cells in comparison with animals trained on the hippocampus-independent task. This increase was abolished by sleep restriction that caused overall reduced cell survival in all animals. Sleep restriction also selectively impaired spatial learning while performance in the nonspatial task was, surprisingly, improved. Further analysis showed that in both training groups fully rested animals applied a spatial strategy irrespective of task requirements; this strategy interfered with performance in the nonspatial task. Conversely, in sleep-restricted animals, this preferred spatial strategy was eliminated, favoring the use of nonspatial information, and hence improving performance in the nonspatial task. These findings suggest that sleep loss altered behavioral strategies to those that do not depend on the hippocampus, concomitantly reversing the neurogenic effects of hippocampus-dependent learning.
Animals↗
Septotemporal distribution of entorhinal projections to the hippocampus in the cat: electrophysiological evidence.
The projection of the entorhinal cortex (EA) to the hippocampus in the cat has been studied by electrophysiological methods. Field potentials elicited by EA stimulation sites were measured in the hippocampus (fascia dentata). Different topographic distributions of the amplitude and of the onset latency of average evoked potentials (AEPs) were obtained depending on the place of the stimulation along a lateromedial axis in the Ea. The lateral EA elicited the largest AEPs in the septal part of the hippocampus and the medial EA evoked maximal responses in the temporal part of the hippocampus, while the intermediate part of the EA evoked the largest AEPs in the splenial (intermediate) part of the hippocampus. Unit activity elicited by hippocampal stimulation was measured in the EA. Analysis of the antidromic unit activity showed that the pathways analysed were monosynaptic. Different conduction velocities to the septal part of the hippocampus were found; the pathway from the lateral EA was the fastest and the pathway from the medial EA the slowest. Assuming that the sites of maximal AEP amplitude correspond to the location of the major synaptic inputs, it can be concluded that the active synaptic inputs arising along a latero-medial axis in the EA are distributed within the hippocampus according to a septotemporal axis, although with some overlap between the different projections. Therefore it may be concluded that the hippocampus is not homogeneous with respect to the inputs from the EA. The present observations are discussed regarding anatomical data and putative functional differences between septal and temporal hippocampus.
Afferent Pathways↗