The oscillatory activity of hippocampal neuronal networks is believed to play a role in memory acquisition and consolidation. Particular focus has been given to characterising theta (4-12 Hz), gamma (40-100 Hz) and ripple (150-250 Hz) oscillations. Beyond these well-described network states, few studies have investigated hippocampal beta2 (23-30 Hz) activity in vivo and its link to behaviour. A previous sudy showed that the exploration of novel environments may lead to the appearance of beta2 oscillations in the mouse hippocampus. In the present study we characterised hippocampal beta2 oscillations in mice during an object recognition task. We found prominent bursts of beta2 oscillations in the beginning of novel exploration sessions (four new objects), which could be readily observed by spectral analysis and visual inspection of local field potentials. Beta2 modulated hippocampal but not neocortical neurons and its power decreased along the session. We also found increased beta2 power in the beginning of a second exploration session performed 24 h later in a slightly modified environment (two new, two familiar objects), but to a lesser extent than in the first session. However, the increase in beta2 power in the second exploration session became similar to the first session when we pharmacologically impaired object recognition in a new set of experiments performed 1 week later. Our results suggest that hippocampal beta2 activity is associated with a dynamic network state tuned for novelty detection and which may allow new learning to occur.

Dopamine and sleep have been independently linked with hippocampus-dependent learning. Since D2 dopaminergic transmission is required for the occurrence of rapid-eye-movement (REM) sleep, it is possible that dopamine affects learning by way of changes in post-acquisition REM sleep. To investigate this hypothesis, we first assessed whether D2 dopaminergic modulation in mice affects novel object preference, a hippocampus-dependent task. Animals trained in the dark period, when sleep is reduced, did not improve significantly in performance when tested 24h after training. In contrast, animals trained in the sleep-rich light period showed significant learning after 24h. When injected with the D2 inverse agonist haloperidol immediately after the exploration of novel objects, animals trained in the light period showed reduced novelty preference upon retesting 24h later. Next we investigated whether haloperidol affected the protein levels of plasticity factors shown to be up-regulated in an experience-dependent manner during REM sleep. Haloperidol decreased post-exploration hippocampal protein levels at 3h, 6h and 12h for phosphorylated Ca(2+)/calmodulin-dependent protein kinase II, at 6h for Zif-268; and at 12h for the brain-derived neurotrophic factor. Electrophysiological and kinematic recordings showed a significant decrease in the amount of REM sleep following haloperidol injection, while slow-wave sleep remained unaltered. Importantly, REM sleep decrease across animals was strongly correlated with deficits in novelty preference (Rho=0.56, p=0.012). Altogether, the results suggest that the dopaminergic regulation of REM sleep affects learning by modulating post-training levels of calcium-dependent plasticity factors.

In this work we devise a classification of mouse activity patterns based on accelerometer data using Detrended Fluctuation Analysis. We use two characteristic mouse behavioural states as benchmarks in this study: waking in free activity and slow-wave sleep (SWS). In both situations we find roughly the same pattern: for short time intervals we observe high correlation in activity - a typical 1/f complex pattern - while for large time intervals there is anti-correlation. High correlation of short intervals ( to : waking state and to : SWS) is related to highly coordinated muscle activity. In the waking state we associate high correlation both to muscle activity and to mouse stereotyped movements (grooming, waking, etc.). On the other side, the observed anti-correlation over large time scales ( to : waking state and to : SWS) during SWS appears related to a feedback autonomic response. The transition from correlated regime at short scales to an anti-correlated regime at large scales during SWS is given by the respiratory cycle interval, while during the waking state this transition occurs at the time scale corresponding to the duration of the stereotyped mouse movements. Furthermore, we find that the waking state is characterized by longer time scales than SWS and by a softer transition from correlation to anti-correlation. Moreover, this soft transition in the waking state encompass a behavioural time scale window that gives rise to a multifractal pattern. We believe that the observed multifractality in mouse activity is formed by the integration of several stereotyped movements each one with a characteristic time correlation. Finally, we compare scaling properties of body acceleration fluctuation time series during sleep and wake periods for healthy mice. Interestingly, differences between sleep and wake in the scaling exponents are comparable to previous works regarding human heartbeat. Complementarily, the nature of these sleep-wake dynamics could lead to a better understanding of neuroautonomic regulation mechanisms.

h i g h l i g h t s• Heterozygous mice for dopamine transporter (DAT+/−) exhibit higher levels of synaptic dopamine.• Here we confirmed that D2 antagonism can interfere in object recognition.• We observed in DAT+/− a natural phenotype of impaired novel object memory recognition.• The injection of haloperidol at 0.05 mg before object exposition restored object recognition.• This effect could be explained by restoring D2 activity to optimal levels, acting on memory acquisition. a r t i c l e i n f o Genetically-modified mice without the dopamine transporter (DAT) are hyperdopaminergic, and serve as models for studies of addiction, mania and hyperactive disorders. Here we investigated the capacity for object recognition in mildly hyperdopaminergic mice heterozygous for DAT (DAT +/−), with synaptic dopaminergic levels situated between those shown by DAT −/− homozygous and wild-type (WT) mice. We used a classical dopamine D2 antagonist, haloperidol, to modulate the levels of dopaminergic transmission in a dose-dependent manner, before or after exploring novel objects. In comparison with WT mice, DAT +/− mice showed a deficit in object recognition upon subsequent testing 24 h later. This deficit was compensated by a single 0.05 mg/kg haloperidol injection 30 min before training. In all mice, a 0.3 mg/kg haloperidol injected immediately after training impaired object recognition. The results indicate that a mild enhancement of dopaminergic levels can be detrimental to object recognition, and that this deficit can be rescued by a low dose of a D2 dopamine receptor antagonist. This suggests that novel object recognition is optimal at intermediate levels of D2 receptor activity.© 2016 Elsevier B.V. All rights reserved.Dopamine (DA) is a neurotransmitter related to complex behaviors, such as: reward perception, social interaction [1,2], and is also linked to memory consolidation both in humans and rodents [3]. Alterations in DA synaptic regulation are related to a large variety of mental diseases, such as schizophrenia, hyperactivity, mood disorders, and Parkinson disease [4,5]. * Corresponding author.E-mail addresses: brunolobaosoares@gmail.com, brunolobaosoares@hotmail.com (B. Lobão-Soares).DA has many receptor subtypes, but they are basically divided in D1 and D2 families [3]. DA, mainly through D1 receptors, elicits the onset of the late phase of long term potentiation in the hippocampus [6], control plasticity-induced protein synthesis [6], and enhance the persistence of hippocampus-dependent memories [7].The involvement of both dopamine receptors families with learning and memory is widely reported for working memory [3], spatial learning [3,6], aversive memory [7], reward-related learning [8] and cognitive flexibility [9]. In particular, impairment in object recognition has been induced by D2 activity suppression due to haloperidol IP injection [10], by D1 activity suppression trough http://dx