Retrieval of stored network activity pattern has been shown as a competitive transition from one attractor state to another, orchestrated by local theta oscillation. However, the fine nature of this process that is considered as substrate of memory recall is not clear. We found that hippocampal network recall is characterized by hyperactivity in the CA3 place cell population, associated with an "overexpression" of the retrieved network pattern. The overexpression was based on recruitment of cells from the same (recalled) spatial representation with low expected firing probability at the given position. We propose that increased place cell activation during state transitions might facilitate pattern completion towards the retrieved network state and stabilize its expression in the network. Furthermore, we observed frequent mixing of both activity patterns at the temporal level of a single theta cycle. On a sub-theta cycle scale, we found signs of segregation that might correspond to a gamma oscillation patterning, as well as occasional mixing at intervals of less than 5 milliseconds. Such short timescale coactivity might induce plasticity mechanisms, leading to associations across the two originally decorrelated network activity states.
- MeSH
- akční potenciály fyziologie MeSH
- hipokampální oblast CA3 patofyziologie MeSH
- modely neurologické * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The hippocampus and retrosplenial cortex are integrated within a higher-order cognitive circuit supporting relational (spatial, contextual, episodic) forms of learning and memory. Hippocampal place cells can coordinate multiple parallel representations in the same physical environment. Novel environment exploration triggers expression of immediate-early genes (IEGs) Arc and Homer1a in spatial context-specific ensembles of CA1 and CA3 neurons. Less is know about ensemble coding in the retrosplenial cortex (RSC), a region directly connected and functionally coupled to CA1. Hippocampal and retrosplenial damage is found in patients with schizophrenia alongside cognitive deficits affecting relational memory. Systemic administration of non-competitive NMDAR antagonists such as MK-801 is used to model psychosis in animals and humans. Acute systemic MK-801 (0.15 mg/kg) impaired cognitive control in rats and ensemble code for spatial context in CA1. Here, we use expression of immediate-early genes Arc and Homer 1a to examine ensemble coding in rat CA3 and RSC to test if the effect of MK-801 extends upstream and downstream of CA1, respectively. Different rats explored the same context twice (A/A), explored two distinct contexts (A/B) or remained in their home cage (CC). In contrast to CA1, MK-801 did not affect ensemble coding in CA3. Unlike CA3 and CA1, similarity of RSC ensembles active during exploration did not reflect change in spatial context, but MK-801 (0.15 mg/kg) increased similarity in RSC ensembles active during spontaneous behavior in the home cage. The data provide support for MK-801-induced functional uncoupling between CA3 and CA1 and suggest that ensemble coding deficit may extend downstream of CA1. This deficit may reflect hyperassociative state in the cognitive circuit underlying cognitive disorganization in psychosis. © 2016 Wiley Periodicals, Inc.
- MeSH
- antagonisté excitačních aminokyselin farmakologie MeSH
- bydlení zvířat MeSH
- cytoskeletální proteiny metabolismus MeSH
- dizocilpinmaleát farmakologie MeSH
- exprese genu účinky léků MeSH
- hipokampální oblast CA1 účinky léků metabolismus MeSH
- hipokampální oblast CA3 účinky léků metabolismus MeSH
- Homer scaffold proteiny metabolismus MeSH
- kognice účinky léků fyziologie MeSH
- mozková kůra účinky léků metabolismus MeSH
- nervové dráhy účinky léků metabolismus MeSH
- pátrací chování účinky léků fyziologie MeSH
- potkani Long-Evans MeSH
- proteiny nervové tkáně metabolismus MeSH
- vnímání prostoru účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The contribution of hippocampal circuits to high-capacity episodic memory is often attributed to the large number of orthogonal activity patterns that may be stored in these networks. Evidence for high-capacity storage in the hippocampus is missing, however. When animals are tested in pairs of environments, different combinations of place cells are recruited, consistent with the notion of independent representations. However, the extent to which representations remain independent across larger numbers of environments has not been determined. To investigate whether spatial firing patterns recur when animals are exposed to multiple environments, we tested rats in 11 recording boxes, each in a different room, allowing for 55 comparisons of place maps in each animal. In each environment, activity was recorded from neuronal ensembles in hippocampal area CA3, with an average of 30 active cells per animal. Representations were highly correlated between repeated tests in the same room but remained orthogonal across all combinations of different rooms, with minimal overlap in the active cell samples from each environment. A low proportion of cells had activity in many rooms but the firing locations of these cells were completely uncorrelated. Taken together, the results suggest that the number of independent spatial representations stored in hippocampal area CA3 is large, with minimal recurrence of spatial firing patterns across environments.
- MeSH
- chování zvířat fyziologie MeSH
- hipokampální oblast CA3 fyziologie MeSH
- krysa rodu rattus MeSH
- mapování mozku * MeSH
- nervová síť fyziologie MeSH
- potkani Long-Evans MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- elektroencefalografie MeSH
- hipokampální oblast CA3 anatomie a histologie fyziologie MeSH
- krysa rodu rattus MeSH
- mozkové vlny fyziologie MeSH
- paměť * fyziologie klasifikace MeSH
- pyramidové buňky fyziologie MeSH
- rozpomínání fyziologie MeSH
- Check Tag
- krysa rodu rattus MeSH
- Publikační typ
- práce podpořená grantem MeSH
Intellectual disability affects 2-3% of the population; mutations of the X-chromosome are a major cause of moderate to severe cases. The link between the molecular consequences of the mutation and impaired cognitive function remains unclear. Loss of function mutations of oligophrenin-1 (OPHN1) disrupt Rho-GTPase signalling. Here we demonstrate abnormal neurotransmission at CA3 synapses in hippocampal slices from Ophn1-/y mice, resulting from a substantial decrease in the readily releasable pool of vesicles. As a result, synaptic transmission fails at high frequencies required for oscillations associated with cognitive functions. Both spontaneous and KA-induced gamma oscillations were reduced in Ophn1-/y hippocampal slices. Spontaneous oscillations were rapidly rescued by inhibition of the downstream signalling pathway of oligophrenin-1. These findings suggest that the intellectual disability due to mutations of oligophrenin-1 results from a synaptopathy and consequent network malfunction, providing a plausible mechanism for the learning disabilities. Furthermore, they raise the prospect of drug treatments for affected individuals.
- MeSH
- cytoskeletální proteiny genetika MeSH
- gama rytmus EEG * MeSH
- hipokampální oblast CA3 metabolismus patofyziologie MeSH
- jaderné proteiny genetika MeSH
- mentální retardace genetika patofyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nervový přenos * MeSH
- proteiny aktivující GTPasu genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Domoic acid (DA) is a potent marine neurotoxine present in seafood. Intoxication by DA causes gastrointestinal symptoms like vomiting and diarrhoea and also the so-called amnesic shellfish poisoning (inflicting memory impairment and seizures). Since exposure to non-convulsive doses is relevant to the human health, we investigated the effect of low dose DA administration in adult Wistar rats. Rats were administered with DA at the dose 1.0 mg/kg and their behavior was monitored for one hour in three sessions. The first session started immediately after DA administration. The second and third session started one and two weeks later. After the third session, the histochemical analysis of the hippocampi of the animals was conducted (Fluoro-Jade B, bis-benzimide). DA increased time spent by locomotion and distance travelled in the second half of the first session and this effect was pronounced during the second and third session. Exploratory rearing was decreased by DA administration in the first half of the first session. DA influenced the grooming in biphasic manner (decrease followed by an increase of time spent by grooming). This biphasic trend was observed even two weeks after the DA administration. Histochemistry of DA treated rats did not confirm the presence of apoptotic bodies, Fluoro-Jade B positive cells were not found neither in CA1 nor CA3 area of the hippocampi. Our study revealed that a low dose of DA affect short and long-term the spontaneous behavior of rats without inducing neuronal damage.
- MeSH
- apoptóza účinky léků MeSH
- depolarizující myorelaxancia aplikace a dávkování toxicita MeSH
- hipokampální oblast CA1 cytologie účinky léků MeSH
- hipokampální oblast CA3 cytologie účinky léků MeSH
- kyselina kainová aplikace a dávkování analogy a deriváty toxicita MeSH
- lokomoce účinky léků MeSH
- náhodné rozdělení MeSH
- péče o zevnějšek u zvířat účinky léků MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Súhrn Východiska: Cieľom práce je študovať účinok ionizujúceho žiarenia na populáciu buniek, ktorá sa podieľa na zložení hipokampálnej formácie v mozgu dospelého potkana. Materiál a metodika: V experimente sme ožiarili dospelé samce potkanov kmeňa Wistar celotelovou frakcionovanou dávkou gama žiarenia (celková dávka 4 Gy). Po uplynutí zvolených časových intervalov (30, 60 a 90 dní po ožiarení) sme pomocou imunohistochemického farbenia identifikovali bunkové typy, ktoré sa nachádzajú v oblastiach CA1, CA3 hipokampu a v priľahlých vrstvách. Pomocou markera Ki-67 sme identifikovali proliferujúce bunky a na detekciu astrocytov sme použili marker GFAP. Výsledky: Pozoruhodný nárast v počte Ki-67-pozitívnych buniek sme zaznamenali tridsať dní po ožiarení, ktorý bol následne vystriedaný ich výrazným poklesom do 60. dňa po expozícii, najmä v oblasti CA1 a opätovným miernym nárastom do 90. dňa po radiačnom zásahu. V počte astrocytov sme zaznamenali ich dočasný úbytok tridsať dní po ožiarení a následné zvýšenie do 60. dňa. V poslednej skupine, ktorá prežívala deväťdesiat dní po expozícii, sme zistili sekundárny pokles GFAP-pozitívnych buniek v obidvoch sledovaných oblastiach. Záver: Výsledky poukazujú na to, že postradiačná odpoveď neurónov a astrocytov, ktoré sa podieľajú na zložení hippokampu, môže zohrávať určitú úlohu vo vývoji neskorých postradiačných prejavov, ktoré sú z hľadiska prognózy nepriaznivejšie.
Backgrounds: The aim of the present study was to investigate the effect of ionizing radiation on the cell population that co-forms hippocampal formation in an adult rat brain. Materials and Methods: Adult male Wistar rats were exposed to whole-body irradiation with fractionated doses of gamma rays (the total dose of 4 Gy). Thirty, 60 and 90 days after irradiation the cell-specific types housed in the CA1, CA3 subregions and adjacent layers were labelled using immunohistochemistry for specific cell phenotypes; Ki-67 marker was used for proliferating cells and GFAP for detection of astrocytes. Results: During the 30th day post-exposure, a considerable increase in the numbers of Ki-67-positive cells was seen. Moreover, significant decline in the density of neurons, mostly in the CA1 subregion, was observed on the 60th day. Slight overaccumulation of Ki-67-positive cells was seen in CA1 area 90 days after radiation treatment. Temporary decrease of GFAP-positive astrocytes was seen thirty days after irradiation, followed by their subsequent increase 60 days after exposure. Secondary decrease of GFAP-positive cells in both of regions was found in the group surviving 90 days post-irradiation. Conclusion: Results showed that radiation response of neurons and astrocytes that form the adult hippocampus may play contributory role in the development of prognostically unfavourable adverse radiation-induced late effect.
- MeSH
- antigen Ki-67 účinky léků účinky záření MeSH
- astrocyty účinky léků účinky záření MeSH
- biologie buňky MeSH
- celotělové ozáření MeSH
- dávka záření MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- hipokampální oblast CA1 cytologie účinky záření MeSH
- hipokampální oblast CA2 cytologie účinky záření MeSH
- hipokampální oblast CA3 cytologie účinky záření MeSH
- hipokampus cytologie účinky záření zranění MeSH
- imunohistochemie metody využití MeSH
- potkani Wistar MeSH
- proliferace buněk účinky záření MeSH
- proteiny nervové tkáně diagnostické užití účinky záření MeSH
- statistika jako téma MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
The strength of an excitatory synapse depends on its ability to release glutamate and on the density of postsynaptic receptors. Genetically encoded glutamate indicators (GEGIs) allow eavesdropping on synaptic transmission at the level of cleft glutamate to investigate properties of the release machinery in detail. Based on the sensor iGluSnFR, we recently developed accelerated versions of GEGIs that allow investigation of synaptic release during 100-Hz trains. Here, we describe the detailed procedures for design and characterization of fast iGluSnFR variants in vitro, transfection of pyramidal cells in organotypic hippocampal cultures, and imaging of evoked glutamate transients with two-photon laser-scanning microscopy. As the released glutamate spreads from a point source-the fusing vesicle-it is possible to localize the vesicle fusion site with a precision exceeding the optical resolution of the microscope. By using a spiral scan path, the temporal resolution can be increased to 1 kHz to capture the peak amplitude of fast iGluSnFR transients. The typical time frame for these experiments is 30 min per synapse.
- MeSH
- biosenzitivní techniky metody MeSH
- hipokampální oblast CA3 cytologie MeSH
- konfokální mikroskopie MeSH
- kultivované buňky MeSH
- kyselina glutamová analýza chemie metabolismus MeSH
- lidé MeSH
- molekulární sondy analýza chemie genetika metabolismus MeSH
- nervový přenos genetika fyziologie MeSH
- optické zobrazování MeSH
- transfekce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Ecstasy or MDMA as a psychoactive drug and hallucinogen is considered one of the most commonly used drugs in the world. This psychotropic substance is discussed both as sexually stimulating and reducing fear and anxiety. Amphetamines also destroy neurons in some brain areas. The aim of this study was to investigate the effects of MDMA on anxiety and apoptosis of hippocampal neurons. Forty-two male Wistar rats of mean weight 200-220 g were used and distributed into six groups [control, control-saline, and experimental groups (1.25, 2.5, 5, 10 mg/kg)]. Rats in experimental groups received MDMA at different doses for seven days by intraperitoneal injection and the control-saline group received saline (1 ml/kg); anxiety was then investigated by plus-maze test. Forty-eight hours after behavioural testing brains were taken from animals and fixed, and after tissue processing, slices were stained with TUNEL kit for apoptotic cells. The area densities of apoptotic neurons were measured throughout the hippocampus and compared in all groups (P < 0.05). Physiological studies showed that 1.25 mg/kg and 2.5 mg/kg doses caused anti-anxiety behaviour and 5 and 10 mg/kg doses of MDMA caused anxietylike behaviour. Moreover, our histological study showed that ecstasy increased apoptotic cell numbers and the highest increase was observed with the 10 mg/kg dose of MDMA. We concluded that MDMA can cause different responses of anxiety-like behaviour in different doses. This phenomenon causes a different ratio of apoptosis in hippocampal formation. Reduction of anxiety-like behaviour induced by the 2.5 mg/kg dose of MDMA can control apoptosis.
- MeSH
- apoptóza * MeSH
- chování zvířat MeSH
- gyrus dentatus patologie MeSH
- hipokampální oblast CA1 patologie MeSH
- hipokampální oblast CA3 patologie MeSH
- hipokampus patologie MeSH
- koncové značení zlomů DNA in situ MeSH
- N-methyl-3,4-methylendioxyamfetamin MeSH
- neurony patologie MeSH
- počet buněk MeSH
- potkani Wistar MeSH
- úzkost chemicky indukované patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
