Grid cells in parahippocampal cortices fire at vertices of a periodic triangular grid that spans the entire recording environment. Such precise neural computations in space have been proposed to emerge from equally precise temporal oscillations within cells or within the local neural circuitry. We found that grid-like firing patterns in the entorhinal cortex vanished when theta oscillations were reduced after intraseptal lidocaine infusions in rats. Other spatially modulated cells in the same cortical region and place cells in the hippocampus retained their spatial firing patterns to a larger extent during these periods without well-organized oscillatory neuronal activity. Precisely timed neural activity within single cells or local networks is thus required for periodic spatial firing but not for single place fields.

Summary The hippocampus generates distinct neural codes to disambiguate similar experiences, a process thought to underlie episodic memory function. Entorhinal grid cells provide a prominent spatial signal to hippocampus, and changes in their firing pattern could thus generate a distinct spatial code in each context. We examined whether we would preclude the emergence of new spatial representations in a novel environment during muscimol inactivation of the medial septal area, a manipulation known to disrupt theta oscillations and grid cell firing. We found that new, highly distinct configurations of place fields emerged immediately and remained stable during the septal inactivation. The new place code persisted when theta oscillations had recovered. Theta rhythmicity and feedforward input from grid cell networks were thus not required to generate new spatial representations in the hippocampus.

This study investigated long-term behavioral, neurochemical, and neuropharmacological effects of ethanol-(7)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) combinations. Over 4 consecutive days, male Long-Evans rats received 1.5 g/kg ethanol and/or 10 mg/kg MDMA, or saline. Rectal temperatures were taken in some rats. Starting 4 days after the last injection, we tested working memory, sensory-motor coordination, and anxiety. Subsequently, we measured cortical, striatal, septal, and hippocampal monoamines (last MDMA injection-euthanasia delay: 20 days), or electrically evoked release of serotonin (5-HT) in cortical and hippocampal slices, and its modulation in the presence of CP 93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrollo[3,2-b]pyrid-5-one) or methiotepin (last MDMA injection-euthanasia delays: 3-6 weeks). Ethanol attenuated the MDMA-induced hyperthermia, but only on the first day. In the longterm, MDMA reduced 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content in most brain regions. The behavioral and neurochemical effects of the ethanol-MDMA combination were comparable to those of MDMA alone; sensory-motor coordination was altered after ethanol and/or MDMA. In hippocampal slices from rats given ethanol and MDMA, the CP 93,129-induced inhibition and methiotepininduced facilitation of 5-HT release were stronger and weaker, respectively, than in the other groups. This is the first study addressing long-term effects of repeated MDMA and EtOH combined treatments in experimental animals. Whereas the drug combination produced the same behavioral and neurochemical effects as MDMA alone, our neuropharmacological results suggest that MDMA-EtOH interactions may have specific long-term consequences on presynaptic modulation of hippocampal 5-HT release, but not necessarily related to MDMA-induced depletion of 5-HT. Thus, it is likely that the psycho(patho)logical problems reported by ecstasy users drinking alcohol are not solely due to the consumption of MDMA.

Using Long-Evans rats tested in a water maze, this study assessed the role of 5-HT1A/5-HT7 receptors of the medial septum in encoding, consolidation, and retrieval of spatial information. The testing protocol (acquisition: daily four-trial sessions over three consecutive days; retention: probe trial on day 4) was first validated by showing that intraseptal infusions of lidocaine (LIDO; 40 microg/0.5 microL) disrupted acquisition and retrieval of the task. 8-OH-DPAT (4 microg/0.5 microL) infused before each acquisition session prevented learning/retention of the platform location, an effect attenuated by pretreatment with the 5-HT1A receptor antagonist WAY 100635. With the 5-HT7 antagonist SB 269970, the 8-OH-DPAT-induced acquisition deficit seemed attenuated, but there was no subsequent retention. When infused immediately, 1, 4, or 6 h after each acquisition session, 8-OH-DPAT did not hinder consolidation. When the infusions were performed 2 h postacquisition, however, consolidation was disrupted. Finally, when infused before a probe trial after drug-free acquisition, 8-OH-DPAT had no effect, suggesting no interference with retrieval processes. We also established that 8-OH-DPAT had no effects when the platform was visible, and altered neither home-cage activity nor anxiety-related behavior (elevated plus-maze). Altogether, these results show that 5-HT1A receptors in the septal region contribute both to declarative-like information encoding and subsequently, within a given postacquisition time window, to its consolidation. They do not participate in the retrieval of recently learned declarative-like information. These observations suggest that 5-HT1A receptors of the medial septum contribute to a serotonin-mediated mechanism involved in the encoding and consolidation, not the retrieval of spatial hippocampal-dependent knowledge. These results might have some relevance to approaches aimed at modifying serotonergic functions in the brain for the treatment of disorders such as depression, anxiety, post-traumatic stress, and amnesia.

3,4-Methylenedioxymethamphetamine [(MDMA) or ecstasy] is a popular club drug often used in combination with ethanol. In the current study, we investigated the effects of MDMA and ethanol combinations on locomotor activity and body temperature of rats. For four consecutive days, male Long-Evans rats were treated daily with a 10-mg/kg dose of MDMA with or without a 1.5-g/kg dose of ethanol. 3,4-Methylenedioxymethamphetamine increased spontaneous activity (on average +1,140%), and this increase was potentiated by ethanol on all days (on average +1,710%). Moreover, ethanol inhibited the MDMA-induced hyperthermia (on average -1.3 degrees C) by the first day of treatment, but not on subsequent treatment days, supporting the suggestion that this effect may undergo tolerance. These observations seem to indicate that combined ethanol-MDMA may induce effects on locomotor activity and thermoregulation that involve separate mechanisms, the first one being less sensitive to tolerance than the second one might be. Results of our study have important implications for understanding the motivation and the health risks of polydrug abusers combining ecstasy and ethanol.

1Animals can flexibly navigate in their environment. This ability is thought to rely on an 2 internal cognitive map. An open question concerns the influence of local sensory cues on the 3 cognitive map and notably their putative contribution to setting its spatial resolution. Here 4 we compared the firing of hippocampal principal cells in mice navigating virtual reality 5 environments in the presence or absence of local visual cues (virtual 3D objects). Objects 6 improved the spatial representation both quantitatively (higher proportion of place cells) 7 and qualitatively (smaller place fields with increased spatial selectivity and stability). This 8 gain in spatial coding resolution was more pronounced near the objects and could be rapidly 9 tuned by their manipulations. In addition, place cells displayed improved theta phase 10 precession in the presence of objects. Thus the hippocampal mapping system can 11 dynamically adjust its spatial coding resolution to local sensory cues available in the 12 environment. 13All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

The ability to flexibly navigate an environment relies on a hippocampal-dependent cognitive map. External space can be internally mapped at different spatial resolutions. However, whether hippocampal spatial coding resolution can rapidly adapt to local features of an environment remains unclear. To explore this possibility, we recorded the firing of hippocampal neurons in mice navigating virtual reality environments, embedding or not local visual cues (virtual 3D objects) in specific locations. Virtual objects enhanced spatial coding resolution in their vicinity with a higher proportion of place cells, smaller place fields, increased spatial selectivity and stability. This effect was highly dynamic upon objects manipulations. Objects also improved temporal coding resolution through improved theta phase precession and theta timescale spike coordination. We propose that the fast adaptation of hippocampal spatial coding resolution to local features of an environment could be relevant for large-scale navigation.

No abstract