Eduard Kelemen

Dynamic Grouping of Hippocampal Neural Activity During Cognitive Control of Two Spatial Frames

Hippocampal neurons represent two concurrent streams of spatial information by transiently organizing into subpopulations of coactive neurons and can reflect the most behaviorally relevant information at any given time.

A hierarchy of neurobehavioral tasks discriminates between mild and moderate brain injury in rats

Behavioral analysis commonly assesses cognitive deficits in rodents following traumatic brain injury (TBI). We examined rats that received sham, mild or moderate injury in the controlled cortical impact model of TBI. The rats were tested in a novel hierarchy of four behavioral tasks with increasing cognitive demand. All three groups had similar performance on the first two phases of training: open field exploration and passive place avoidance using a stationary shock zone on a non-rotating arena. The similar performance on the first two tasks suggested comparable sensory, motor skills and contextual memory in all three groups. In phase three, rats were tested on active place avoidance, their ability to avoid a stationary shock zone on the rotating arena. Control and mildly-injured rats learned this task within four ten-minute trials while moderately-injured animals were impaired. Moderately-injured animals were also impaired if tested 3 weeks after injury. One day after phase three, sham- and mildly-injured animals were tested on a phase four conflict active avoidance task with the shock zone shifted 180 degrees from its phase three location and mildly-injured animals were impaired. The speed in which the animals complete the four phases of testing as well as the ability to discriminate between differing injury severity suggests that this set of neurobehavioral tasks will be useful to understand cognitive deficits underlying TBI as well as a useful screening method for therapeutic drugs.

Key features of human episodic recollection in the cross-episode retrieval of rat hippocampus representations of space.

Using a rat model of episodic memory, the authors show that recollection is not a verbatim replay of stored experience, but is rather an intermingling of stored memory, environmental circumstances, and the subjects state of mind.

Coordinating different representations in the hippocampus

The processes that organize different thoughts and memories, allowing the separation of currently relevant and irrelevant information, are collectively known as cognitive control. The neuronal mechanisms of these processes can be investigated by place cell ensemble recordings during behaviors and environmental manipulations that present cognitive control challenges to selectively represent one of multiple possible alternative estimates of location. We review place cell studies that investigate responses to manipulations that dissociate the environment into two or more spatial frames of locations, often times to test notions of pattern separation. Manipulations, such as continuously rotating the recording chamber reveal that the ensemble discharge in hippocampus self-organizes into multiple, transiently-organized representations of space, each defined by the subset of coactive cells. Ensemble discharge in the hippocampus alternates between separate representations of frame-specific positions on timescales from 25 ms to several seconds. The dynamic, functional grouping of discharge into transiently co-active subsets of cells is predicted by the animals changing behavioral needs. In addition to identifying neural correlates of cognitive control in hippocampus, these observations demonstrate that the separation of neuronal activity into distinctive representations depends on ongoing cognitive demands and that what can appear as noise, deviations from receptive field tuning, can substantially be the result of these internal knowledge-guided fluctuations. These findings inspire a new perspective that should be taken into account when investigating pattern separation--a perspective that emphasizes changes in hippocampal neural discharge that are happening on a short timescale and does not assume that patterns of neural discharge are steady and stationary across the several minutes of the recordings.

Stress-induced out-of-context activation of memory.

An intensely stressful experience can itself activate memories that are unrelated to the stressful experience. This previously unknown property of stress could help explain how traumatic memories become pathological.

The Organization of Neuronal Discharge on Timescales of Milliseconds and Seconds Is Related to the Spatial Response Properties of Hippocampal Neurons

According to a widely held view, the neuronal discharge underlying cognition is structured into temporally and functionally organized cell assemblies. What timescale(s) this dynamic organization operates on, is an open question. We analyze the relationship between the timing of the discharge amongst hippocampus neurons and the information they process that is manifest in the spatial response properties of these cells. On timescales of tens of milliseconds and seconds, we observed that the firing of cells with similar response properties is positively correlated, while the firing of cells with distinct response properties is uncorrelated or negatively correlated. Our results show that neuronal discharge is organized on a range of timescales, which may serve distinct functions.

Phencyclidine discoordinates hippocampal network activity but not place fields

We used the psychotomimetic phencyclidine (PCP) to investigate the relationships among cognitive behavior, coordinated neural network function, and information processing within the hippocampus place cell system. We report in rats that PCP (5 mg/kg, i.p.) impairs a well learned, hippocampus-dependent place avoidance behavior in rats that requires cognitive control even when PCP is injected directly into dorsal hippocampus. PCP increases 60–100 Hz medium-freguency gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive impairment caused by systemic PCP administration. PCP discoordinates theta-modulated medium-frequency and slow gamma oscillations in CA1 LFPs such that medium-frequency gamma oscillations become more theta-organized than slow gamma oscillations. CA1 place cell firing fields are preserved under PCP, but the drug discoordinates the subsecond temporal organization of discharge among place cells. This discoordination causes place cell ensemble representations of a familiar space to cease resembling pre-PCP representations despite preserved place fields. These findings point to the cognitive impairments caused by PCP arising from neural discoordination. PCP disrupts the timing of discharge with respect to the subsecond timescales of theta and gamma oscillations in the LFP. Because these oscillations arise from local inhibitory synaptic activity, these findings point to excitation–inhibition discoordination as the root of PCP-induced cognitive impairment. SIGNIFICANCE STATEMENT Hippocampal neural discharge is temporally coordinated on timescales of theta and gamma oscillations in the LFP and the discharge of a subset of pyramidal neurons called “place cells” is spatially organized such that discharge is restricted to locations called a cells “place field.” Because this temporal coordination and spatial discharge organization is thought to represent spatial knowledge, we used the psychotomimetic phencyclidine (PCP) to disrupt cognitive behavior and assess the importance of neural coordination and place fields for spatial cognition. PCP impaired the judicious use of spatial information and discoordinated hippocampal discharge without disrupting firing fields. These findings dissociate place fields from spatial cognitive behavior and suggest that hippocampus discharge coordination is crucial to spatial cognition.

Impairment of neural coordination in hippocampal neuronal ensembles after a psychotomimetic dose of dizocilpine

&NA; The discoordination hypothesis of schizophrenia posits discoordination of neural activity as the central mechanism that underlies some psychotic symptoms (including ‘hallmark’ cognitive symptoms) of schizophrenia. To test this proposition, we studied the activity of hippocampal neurons in urethane anesthetized Long Evans rats after 0.15 mg/kg dizocilpine (MK‐801), an N‐Methyl‐d‐aspartate (NMDA) glutamate receptor antagonist, which can cause psychotic symptoms in humans and cognitive control impairments in animals. We observed that MK‐801 altered the temporal coordination, but not rate, of neuronal firing. Coactivation between neurons increased, driven primarily by increased coincident firing of cell pairs that did not originally fire together before MK‐801 injection. Increased pairwise coactivation manifested as disorganized discharge on the level of neuronal ensembles, which in turn could lead to disorganization in information processing. Disorganization of neuronal activity after a psychotomimetic dose of MK‐801 supports the discoordination hypothesis of psychosis. HighlightsEffect of psychotomimetic MK‐801 on activity of hippocampal neurons was studied.MK‐801 altered the temporal coordination, but not rate, of neuronal firing.MK‐801 increased coincident firing of cell pairs that did not fire together before.The number of theta modulated neurons increased after MK‐801.The findings support discoordination hypothesis of psychosis.

Transient inactivation of the anterior cingulate cortex in rats disrupts avoidance of a dynamic object

Although animals often learn and monitor the spatial properties of relevant moving objects such as conspecifics and predators to properly organize their own spatial behavior, the underlying brain substrate has received little attention and hence remains elusive. Because the anterior cingulate cortex (ACC) participates in conflict monitoring and effort-based decision making, and ACC neurons respond to objects in the environment, it may also play a role in the monitoring of moving cues and exerting the appropriate spatial response. We used a robot avoidance task in which a rat had to maintain at least a 25cm distance from a small programmable robot to avoid a foot shock. In successive sessions, we trained ten Long Evans male rats to avoid a fast-moving robot (4cm/s), a stationary robot, and a slow-moving robot (1cm/s). In each condition, the ACC was transiently inactivated by bilateral injections of muscimol in the penultimate session and a control saline injection was given in the last session. Compared to the corresponding saline session, ACC-inactivated rats received more shocks when tested in the fast-moving condition, but not in the stationary or slow robot conditions. Furthermore, ACC-inactivated rats less frequently responded to an approaching robot with appropriate escape responses although their response to shock stimuli remained preserved. Since we observed no effect on slow or stationary robot avoidance, we conclude that the ACC may exert cognitive efforts for monitoring dynamic updating of the position of an object, a role complementary to the dorsal hippocampus.