There has been considerable research showing populations of neurons encoding for different aspects of space in the brain. Recently, several studies using two-photon calcium imaging and virtual navigation have identified "spatially" modulated neurons in the posterior cortex. We enquire here whether the presence of such spatial representations may be a cortex-wide phenomenon and, if so, whether these representations can be organized in the absence of the hippocampus. To this end, we imaged the dorsal cortex of mice running on a treadmill populated with tactile cues. A high percentage (40-80%) of the detected neurons exhibited sparse, spatially localized activity, with activity fields uniformly localized over the track. The development of this location specificity was impaired by hippocampal damage. Thus, there is a substantial population of neurons distributed widely over the cortex that collectively form a continuous representation of the explored environment, and hippocampal outflow is necessary to organize this phenomenon.

The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group SE+CBDt), and compared to rats submitted only to SE (SE group), CBD, or vehicle (VH group). Groups were evaluated during SE (behavioral and electrophysiological analysis), as well as at days one and three post-SE (exploratory activity, electrophysiological analysis, neuron density, and neuron degeneration). Compared to SE group, SE+CBD groups (SE+CBDp and SE+CBDt) had increased SE latency, diminished SE severity, increased contralateral afterdischarge latency and decreased relative powers in delta (0.5–4 Hz) and theta (4–10 Hz) bands. Only SE+CBDp had increased vertical exploratory activity 1-day post SE and decreased contralateral relative power in delta 3 days after SE, when compared to SE group. SE+CBD groups also showed decreased neurodegeneration in the hilus and CA3, and higher neuron density in granule cell layer, hilus, CA3, and CA1, when compared to SE group. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders.

No abstract

The brain likely uses offline periods to consolidate recent memories. One hypothesis holds that the hippocampal output provides a unique, global linking or ‘index’ code for each memory, and that this code is stored in the cortex in association with locally encoded attributes of each memory. Activation of the index code is hypothesized to evoke coordinated memory trace reactivation thus facilitating consolidation. Retrosplenial cortex (RSC) is a major recipient of hippocampal outflow and we have described populations of neurons there with sparse and orthogonal coding characteristics that resemble hippocampal ‘place’ cells, and whose expression depends on an intact hippocampus. Using two-photon Ca 2+ imaging, we recorded ensembles of neurons in the RSC during periods of immobility before and after active running on a familiar linear treadmill track. Synchronous bursting of distinct groups of neurons occurred during rest both prior to and after running. In the second rest epoch, these patterns were associated with the locations of tactile landmarks and reward. Complementing established views on the functions of the RSC, our findings indicate that the structure is involved with processing landmark information during rest. This article is part of the Theo Murphy meeting issue ‘Memory reactivation: replaying events past, present and future’.

Abstract-Brain glucose metabolism is altered in sporadic Alzheimer's disease (sAD), whose pathologies are reproduced in rodents by intracerebroventricular (icv) infusion of streptozotocin (STZ) in subdiabetogenic doses. The icv-STZ model also culminates in central cholinergic dysfunctions, which in turn are known to underlie both the sAD cognitive decline, and synaptic plasticity impairments. Considering the cognitive-enhancing potential of chronic nicotine (Nic), we investigated whether it attenuates icv-STZ-induced impairments in recognition memory and synaptic plasticity in a cognition-relevant substrate: the hippocampal CA1-medial prefrontal cortex (mPFC) pathway. Rats treated with icv-STZ were submitted to a chronic Nic regime, and were evaluated for recognition memory. We then examined long-term potentiation (LTP), paired-pulse facilitation (PPF) under urethane anesthesia, and brains were also evaluated for hippocampus-mPFC cell density. We found that Nic treatment prevents icv-STZ-induced disruptions in recognition memory and LTP. STZ did not precipitate neuronal death, while Nic alone was associated with higher neuronal density in CA1 when compared to vehicle-injected animals. Through combining behavioral, neurophysiological, and neuropathological observations into the Nic-STZ interplay, our study reinforces that cholinergic treatments are of clinical importance against earlystage Alzheimer's disease and mild cognitive impairments.

Observations of neurons in a resting brain and neurons in cultures often display spontaneous scale-free (SF) collective dynamics in the form of information cascades, also called ‘neuronal avalanches’. This has motivated the so called critical brain hypothesis which posits that the brain is self-tuned to a critical point or regime, separating exponentially-growing dynamics from quiescent states, to achieve optimality. Yet, how such optimality of information transmission is related to behavior and whether it persists under behavioral transitions has remained a fundamental knowledge gap. Here, we aim to tackle this challenge by studying behavioral transitions in mice using two-photon calcium imaging of the retrosplenial cortex (RSC)—an area of the brain well positioned to integrate sensory, mnemonic, and cognitive information by virtue of its strong connectivity with the hippocampus, medial prefrontal cortex, and primary sensory cortices. Our work shows that the response of the underlying neural population to behavioral transitions can vary significantly between different sub-populations such that one needs to take the structural and functional network properties of these sub-populations into account to understand the properties at the total population level. Specifically, we show that the RSC contains at least one sub-population capable of switching between two different SF regimes, indicating an intricate relationship between behavior and the optimality of neuronal response at the subgroup level. This asks for a potential reinterpretation of the emergence of self-organized criticality in neuronal systems.

No abstract

Episodic memory depends on the association of diverse attribute representations that are distributed across the neocortex, and evidence suggests that these attributes are linked, at least initially, by the hippocampus, which orchestrates retrieval and the offline replay of experience during memory consolidation. The dynamics that characterize this hippocampal-cortical dialogue, however, are only partly understood. Although it was originally proposed that replay is initiated in CA3, with the spontaneous emission of sharp-wave ripple (SWR) bursts, increasing evidence suggests that cortex may seed the process with partial information, leading to pattern completion in CA3 and subsequent global reactivation of the episode. A recent study has shown that the secondary motor cortex (M2), among other areas, carries two distinct types of representations: place cell-like activity, which relies on an intact hippocampus for its development, and responses tied to visuo-tactile cues — the 'attributes' of the experience, which do not require the hippocampus. Using two-photon Ca2+imaging, while simultaneously acquiring LFP from the ipsilateral CA1, we assessed the interactions among cortical retrieval of visuo-tactile attributes of previous experiences in a virtual environment, hippocampal SWR, and the cortical reinstatement of the spatial aspects of the same experiences. During rest after the experience, two types of reactivation events occurred, which separately conveyed information about spatial trajectories and visuo-tactile attributes. Reactivation of attribute information preceded that of trajectories in relation to hippocampal SWRs. Furthermore, paired reactivations of cue and trajectory information supported similar features of previous experiences. These results are consistent with the hypothesis that cortical retrieval of non-spatial attributes of recent experience seeds hippocampal reactivation of associated spatial sequences, which is followed by retrieval of episodic memory traces.