Modulation Of Hippocampal Activity Research Articles

Reduced hippocampal-cortical connectivity during memory suppression predicts the ability to forget unwanted memories.

The ability to suppress unwelcome memories is important for productivity and well-being. Successful memory suppression is associated with hippocampal deactivations and a concomitant disruption of this region's functionality. Much of the previous neuroimaging literature exploring such suppression-related hippocampal modulations has focused on the region's negative coupling with the prefrontal cortex. Task-based changes in functional connectivity between the hippocampus and other brain regions still need further exploration. In the present study, we utilize psychophysiological interactions and seed connectome-based predictive modeling to investigate the relationship between the hippocampus and the rest of the brain as 134 participants attempted to suppress unwanted memories during the Think/No-Think task. The results show that during retrieval suppression, the right hippocampus exhibited decreased functional connectivity with visual cortical areas (lingual and cuneus gyrus), left nucleus accumbens and the brain-stem that predicted superior forgetting of unwanted memories on later memory tests. Validation tests verified that prediction performance was not an artifact of head motion or prediction method and that the negative features remained consistent across different brain parcellations. These findings suggest that systemic memory suppression involves more than the modulation of hippocampal activity-it alters functional connectivity patterns between the hippocampus and visual cortex, leading to successful forgetting.

Pharmacologic Modulation of Hippocampal Activity in Psychosis

Pharmacologic Modulation of Hippocampal Activity in Psychosis

The Hippocampal Film Editor: Sensitivity and Specificity to Event Boundaries in Continuous Experience.

The function of the human hippocampus is normally investigated by experimental manipulation of discrete events. Less is known about what triggers hippocampal activity during more naturalistic, continuous experience. We hypothesized that the hippocampus would be sensitive to the occurrence of event boundaries, that is, moments in time identified by observers as a transition between events. To address this, we analyzed functional MRI data from two groups: one (n = 253, 131 female) who viewed an 8.5 min film and another (n = 15, 6 female) who viewed a 120 min film. We observed a strong hippocampal response at boundaries defined by independent observers, which was modulated by boundary salience (the number of observers that identified each boundary). In the longer film, there were sufficient boundaries to show that this modulation remained after covarying out a large number of perceptual factors. This hypothesis-driven approach was complemented by a data-driven approach, in which we identified hippocampal events as moments in time with the strongest hippocampal activity. The correspondence between these hippocampal events and event boundaries was highly significant, revealing that the hippocampal response is not only sensitive, but also specific to event boundaries. We conclude that event boundaries play a key role in shaping hippocampal activity during encoding of naturalistic events.SIGNIFICANCE STATEMENT Recent years have seen the field of human neuroscience research transitioning from experiments with simple stimuli to the study of more complex and naturalistic experience. Nonetheless, our understanding of the function of many brain regions, such as the hippocampus, is based primarily on the study of brief, discrete events. As a result, we know little of what triggers hippocampal activity in real-life settings when we are exposed to a continuous stream of information. When does the hippocampus “decide” to respond during the encoding of naturalistic experience? We reveal here that hippocampal activity measured by fMRI during film watching is both sensitive and specific to event boundaries, identifying a potential mechanism whereby event boundaries shape experience by modulation of hippocampal activity.

Modulation of Hippocampal Activity by Vagus Nerve Stimulation in Freely Moving Rats.

Vagus Nerve Stimulation (VNS) has seizure-suppressing effects but the underlying mechanism is not fully understood. To further elucidate the mechanisms underlying VNS-induced seizure suppression at a neurophysiological level, the present study examined effects of VNS on hippocampal excitability using dentate gyrus evoked potentials (EPs) and hippocampal electroencephalography (EEG). Male Sprague-Dawley rats were implanted with a VNS electrode around the left vagus nerve. A bipolar stimulation electrode was implanted in the left perforant path and a bipolar recording electrode was implanted in the left dentate gyrus for EEG and dentate field EP recording. Following recovery, VNS was applied in freely moving animals, using a duty cycle of 7 s on/18 s off, 30 Hz frequency, 250 µs pulse width, and an intensity of either 0 (SHAM), 25 µA or 1000 µA, while continuously monitoring EEG and dentate field EPs. VNS at 1000 µA modulated dentate field EPs by decreasing the field excitatory post-synaptic potential (fEPSP) slope and increasing the latency and amplitude of the population spike. It additionally influenced hippocampal EEG by slowing theta rhythm from 7 Hz to 5 Hz and reducing theta peak and gamma band power. No effects were observed in the SHAM or 25 µA VNS conditions. VNS modulated hippocampal excitability of freely moving rats in a complex way. It decreased synaptic efficacy, reflected by decreased fEPSP slope and EEG power, but it simultaneously facilitated dentate granule cell discharge indicating depolarization of dentate granule cells.

Nootropic effect of meadowsweet (Filipendula vulgaris) extracts.

The effects of the extracts of the aboveground parts of Filipendula vulgaris Moench on the behavior and memory of mice after hypoxic injury and their physical performance in the open-field test were studied using the models of hypoxia in a sealed volume, conditioned passive avoidance response (CPAR), and forced swimming with a load. The extracts improved animal resistance to hypoxia, normalized orientation and exploration activities, promoted CPAR retention after hypoxic injury, and increased physical performance. Aqueous extract of meadowsweet had the most pronounced effect that corresponded to the effect of the reference drug piracetam. These effects were probably caused by modulation of hippocampal activity.

Cholinergic modulation of hippocampal activity during septic encephalopathy

Septic encephalopathy is a sepsis-related brain dysfunction with a deterioration of cortical functions. The experimental studies in the rat brain revealed a deranged neurotransmitter proflle during septic encephalopathy. Glutamatergic synapses, essential in learning and memory, undergo use-dependent changes in synaptic strength, referred to as plasticity. Permanent strengthening of synapses after a brief stimulus, termed long-term potentiation (LTP), was discovered in the hippocampus, and here it has been most thoroughly studied. Cholinergic neurotransmission plays an important role in regulating the cognitive functions of the brain. It acts as a signal-to-noise ratio modulator of sensory and cognitive inputs. The irregularities in brain functions give rise to the symptoms of delirium, including disorganized thinking and disturbances of attention and consciousness, which in turn might affect learning and memory. Possible mechanisms for cholinergic deficiency include impairment of synaptic functions of acetylcholine. Imbalances in the cholinergic system during sepsis might therefore play an extensive role in the septic delirium.

Corticosteroid actions in the hippocampus.

Corticosteroid hormones can enter the brain and bind to two intracellular receptor types that regulate transcription of responsive genes: (i) the high affinity mineralocorticoid receptors and (ii) the glucocorticoid receptors with approximately 10-fold lower affinity. Although most cells in the brain predominantly express glucocorticoid receptors, principal cells in limbic structures such as the hippocampus often contain glucocorticoid as well as mineralocorticoid receptors. Recent electrophysiological studies have examined the consequences of transcriptional regulation via the two receptor types for information transfer in the hippocampus. It was found that, under resting conditions, corticosteroids do not markedly alter electrical activity. However, if neurones are shifted towards more depolarized or hyperpolarized potentials due to the action of neurotransmitters, slow and adaptive effects of the corticosteroid hormones become apparent. In general, mineralocorticoid receptor occupation maintains steady electrical activity in hippocampal neurones. Brief activation of glucocorticoid receptors leads to increased influx of calcium, which normally helps to slowly reverse temporarily raised electrical activity. These slow and persistent corticosteroid actions will alter network function within the hippocampus, thus contributing to behavioural adaptation in response to stress. Modulation of hippocampal activity by corticosteroids also affects hippocampal output (e.g. to inhibitory interneurones which control hypothalamic-pituitary-adrenal axis activity). The enhanced calcium influx after glucocorticoid receptor activation can become a risk factor when cells are simultaneously exposed to strong depolarizing inputs, such as those occurring during ischaemia. Similarly, chronically elevated corticosteroid levels (or lack of corticosteroids) could endanger hippocampal cell function. The latter may contribute to the precipitation of clinical symptoms in diseases associated with chronically aberrant corticosteroid levels.

Amygdala activity related to enhanced memory for pleasant and aversive stimuli.

Pleasant or aversive events are better remembered than neutral events. Emotional enhancement of episodic memory has been linked to the amygdala in animal and neuropsychological studies. Using positron emission tomography, we show that bilateral amygdala activity during memory encoding is correlated with enhanced episodic recognition memory for both pleasant and aversive visual stimuli relative to neutral stimuli, and that this relationship is specific to emotional stimuli. Furthermore, data suggest that the amygdala enhances episodic memory in part through modulation of hippocampal activity. The human amygdala seems to modulate the strength of conscious memory for events according to emotional importance, regardless of whether the emotion is pleasant or aversive.

Response pattern of cat hippocampal neurons to stimulation of the septal area during sleep and waking

Unitary discharge was recorded extracellularly from cat dorsal hippocampus. The response pattern to electrical stimulation of the septum and regio limbica anterior was examined. There was a definite difference in the response pattern between the basket cell and the theta cell. Cluster analysis of high dimensional data was performed by means of Andrews' function plot. When compared with simple spike cells, complex spike cells showed a greater difference with one another with respect to the variation in the response pattern during different phases of sleep and wakefulness. The response patterns of complex spike cells showed a greater difference with one another during SS and PS than during A. It is suggested that the modulation of hippocampal activity during sleep and wakefulness is, as assessed from the reactivity to septal stimulation, operating more differentially at the output neurons than at its interneurons.