Strategies discovery in the active allothetic place avoidance task.

The Active Allothetic Place Avoidance task is an alternative setup to Morris Water Maze that allows studying spatial memory in a dynamic world in the presence of conflicting information. In this task, a rat, freely moving on a rotating circular arena, has to avoid a sector defined within the room frame where shocks are presented. While for Morris Water Maze several studies have identified animal strategies which specifically affect performance, there were no such studies for the Active Allothetic Place Avoidance task. Using standard machine learning methods, we were able to reveal for the first time, to the best of our knowledge, explainable strategies that the animals employ in this task and demonstrate that they can provide a high-level interpretation for performance differences between an animal group treated with silver nanoparticles (AgNPs) and the control group.

Recognition of post-learning alteration of hippocampal ripples by convolutional neural network differs in the wild-type and AD mice.

Evidence indicates that sharp-wave ripples (SWRs) are primary network events supporting memory processes. However, some studies demonstrate that even after disruption of awake SWRs the animal can still learn spatial task or that SWRs may be not necessary to establish a cognitive map of the environment. Moreover, we have found recently that despite a deficit of sleep SWRs the APP/PS1 mice, a model of Alzheimer's disease, show undisturbed spatial reference memory. Searching for a learning-related alteration of SWRs that could account for the efficiency of memory in these mice we use convolutional neural networks (CNN) to discriminate pre- and post-learning 256 ms samples of LFP signals, containing individual SWRs. We found that the fraction of samples that were correctly recognized by CNN in majority of discrimination sessions was equal to ~ 50% in the wild-type (WT) and only 14% in APP/PS1 mice. Moreover, removing signals generated in a close vicinity of SWRs significantly diminished the number of such highly recognizable samples in the WT but not in APP/PS1 group. These results indicate that in WT animals a large subset of SWRs and signals generated in their proximity may contain learning-related information whereas such information seem to be limited in the AD mice.

Reconfiguration of the cortical-hippocampal interaction may compensate for Sharp-Wave Ripple deficits in APP/PS1 mice and support spatial memory formation.

Hippocampal-cortical dialogue, during which hippocampal ripple oscillations support information transfer, is necessary for long-term consolidation of spatial memories. Whereas a vast amount of work has been carried out to understand the cellular and molecular mechanisms involved in the impairments of memory formation in Alzheimer's disease (AD), far less work has been accomplished to understand these memory deficiencies at the network-level interaction that may underlie memory processing. We recently demonstrated that freely moving 8 to 9-month-old APP/PS1 mice, a model of AD, are able to learn a spatial reference memory task despite a major deficit in Sharp-Wave Ripples (SWRs), the integrity of which is considered to be crucial for spatial memory formation. In order to test whether reconfiguration of hippocampal-cortical dialogue could be responsible for the maintenance of this ability for memory formation, we undertook a study to identify causal relations between hippocampal and cortical circuits in epochs when SWRs are generated in hippocampus. We analyzed the data set obtained from multielectrode intracranial recording of transgenic and wild-type mice undergoing consolidation of spatial memory reported in our previous study. We applied Directed Transfer Function, a connectivity measure based on Granger causality, in order to determine effective coupling between distributed circuits which express oscillatory activity in multiple frequency bands. Our results showed that hippocampal-cortical coupling in epochs containing SWRs was expressed in the two frequency ranges corresponding to ripple (130-180 Hz) and slow gamma (20-60 Hz) band. The general features of connectivity patterns were similar in the 8 to 9-month-old APP/PS1 and wild-type animals except that the coupling in the slow gamma range was stronger and spread to more cortical sites in APP/PS1 mice than in the wild-type group. During the occurrence of SWRs, the strength of effective coupling from the cortex to hippocampus (CA1) in the ripple band undergoes sharp increase, involving cortical areas that were different in the two groups of animals. In the wild-type group, retrosplenial cortex and posterior cingulate cortex interacted with the hippocampus most strongly, whereas in the APP/PS1 group more anterior structures interacted with the hippocampus, that is, anterior cingulate cortex and prefrontal cortex. This reconfiguration of cortical-hippocampal interaction pattern may be an adaptive mechanism responsible for supporting spatial memory consolidation in AD mice model.

Deficit in hippocampal ripples does not preclude spatial memory formation in APP/PS1 mice.

General theory of declarative memory formation posits a cortical-hippocampal dialog during which hippocampal ripple oscillations support information transfer and long-term consolidation of hippocampus dependent memories. Brain dementia, as Alzheimer disease (AD), is accompanied by memory loss and inability to form new memories. A large body of work has shown variety of mechanisms acting at cellular and molecular levels which can putatively play an important role in the impairment of memory formation. However, far less is known about changes occurring at the network-level activity patterns that support memory processing. Using freely moving APP/PS1 mice, a model of AD, we undertook a study to unravel the alterations of the activity of hippocampal and cortical circuits during generation of ripples in the transgenic and wild-type mice undergoing encoding and consolidation of spatial information. We report that APP/PS1 animals are able to consolidate spatial memory despite a major deficit of hippocampal ripples occurrence rate and learning dependent dynamics. We propose that these impairments may be compensated by an increase of the occurrence of cortical ripples and reorganization of cortical-hippocampal interaction.

A Mechanism of Synaptic Clock Underlying Subjective Time Perception.

Temporal resolution of visual information processing is thought to be an important factor in predator-prey interactions, shaped in the course of evolution by animals' particular ecology. Here I show that light can be considered to have a dual role of a source of information, which guides motor actions, and an environmental feedback for those actions. I consequently show how temporal perception might depend on feedback-based behavioral adaptations realized in the nervous system through activity-dependent synaptic plasticity. I propose an underlying mechanism of synaptic clock, with every synapse having its characteristic time unit, determined by the persistence of memory traces of synaptic inputs, which is used by the synapse to tell time, and postulate the existence of a specific brain-wide distribution of synaptic clocks with different time units. The present theory offers a simple, testable link between the fields of neurobiology of memory, time perception and ecology, which may account for numerous experimental findings, including the interspecies variation in the temporal resolution and the properties of subjective time perception in humans, specifically the variable speed of perceived time passage, depending on emotional or attentional states or tasks performed.