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Open accessJournal ArticleDOI: 10.3389/FNCEL.2021.649262

The Theta Rhythm of the Hippocampus: From Neuronal and Circuit Mechanisms to Behavior

04 Mar 2021-Frontiers in Cellular Neuroscience (Frontiers Media SA)-Vol. 15, pp 649262-649262
Abstract: This review focuses on the neuronal and circuit mechanisms involved in the generation of the theta (θ) rhythm and of its participation in behavior. Data have accumulated indicating that θ arises from interactions between medial septum-diagonal band of Broca (MS-DbB) and intra-hippocampal circuits. The intrinsic properties of MS-DbB and hippocampal neurons have also been shown to play a key role in θ generation. A growing number of studies suggest that θ may represent a timing mechanism to temporally organize movement sequences, memory encoding, or planned trajectories for spatial navigation. To accomplish those functions, θ and gamma (γ) oscillations interact during the awake state and REM sleep, which are considered to be critical for learning and memory processes. Further, we discuss that the loss of this interaction is at the base of various neurophatological conditions.

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6 results found

Open accessJournal ArticleDOI: 10.1016/J.EBR.2021.100467
01 Jan 2021-
Abstract: Implanted neurostimulation devices are gaining traction as palliative treatment options for certain forms of drug-resistant epilepsy, but clinical utility of these devices is hindered by incomplete mechanistic understanding of their therapeutic effects. Approved devices for anterior thalamic nuclei deep brain stimulation (ANT DBS) are thought to work at a network level, but limited sensing capability precludes characterization of neurophysiological effects outside the thalamus. Here, we describe a patient with drug-resistant temporal lobe epilepsy who was implanted with a responsive neurostimulation device (RNS System), involving hippocampal and ipsilateral temporal neocortical leads, and subsequently received ANT DBS. Over 1.5 years, RNS System electrocorticography enabled multiscale characterization of neurophysiological effects of thalamic stimulation. In brain regions sampled by the RNS System, ANT DBS produced acute, phasic, frequency-dependent responses, including suppression of hippocampal low frequency local field potentials. ANT DBS modulated functional connectivity between hippocampus and neocortex. Finally, ANT DBS progressively suppressed hippocampal epileptiform activity in relation to the extent of hippocampal theta suppression, which informs stimulation parameter selection for ANT DBS. Taken together, this unique clinical scenario, involving hippocampal recordings of unprecedented chronicity alongside ANT DBS, sheds light on the therapeutic mechanism of thalamic stimulation and highlights capabilities needed in next-generation devices

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1 Citations

Open accessJournal ArticleDOI: 10.3389/FNCEL.2021.732360
Abstract: The hippocampus-prefrontal cortex (HPC-PFC) pathway plays a fundamental role in executive and emotional functions. Neurophysiological studies have begun to unveil the dynamics of HPC-PFC interaction in both immediate demands and long-term adaptations. Disruptions in HPC-PFC functional connectivity can contribute to neuropsychiatric symptoms observed in mental illnesses and neurological conditions, such as schizophrenia, depression, anxiety disorders, and Alzheimer's disease. Given the role in functional and dysfunctional physiology, it is crucial to understand the mechanisms that modulate the dynamics of HPC-PFC communication. Two of the main mechanisms that regulate HPC-PFC interactions are synaptic plasticity and modulatory neurotransmission. Synaptic plasticity can be investigated inducing long-term potentiation or long-term depression, while spontaneous functional connectivity can be inferred by statistical dependencies between the local field potentials of both regions. In turn, several neurotransmitters, such as acetylcholine, dopamine, serotonin, noradrenaline, and endocannabinoids, can regulate the fine-tuning of HPC-PFC connectivity. Despite experimental evidence, the effects of neuromodulation on HPC-PFC neuronal dynamics from cellular to behavioral levels are not fully understood. The current literature lacks a review that focuses on the main neurotransmitter interactions with HPC-PFC activity. Here we reviewed studies showing the effects of the main neurotransmitter systems in long- and short-term HPC-PFC synaptic plasticity. We also looked for the neuromodulatory effects on HPC-PFC oscillatory coordination. Finally, we review the implications of HPC-PFC disruption in synaptic plasticity and functional connectivity on cognition and neuropsychiatric disorders. The comprehensive overview of these impairments could help better understand the role of neuromodulation in HPC-PFC communication and generate insights into the etiology and physiopathology of clinical conditions.

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Topics: Synaptic plasticity (57%), Neuromodulation (medicine) (55%), Long-term potentiation (52%) ... read more

Open accessJournal ArticleDOI: 10.1038/S41598-021-01667-8
Yuko Kondo-Takuma1, Masayuki Mizuno1, Yo Tsuda1, Yuta Madokoro1  +8 moreInstitutions (2)
11 Nov 2021-Scientific Reports
Abstract: The cholinergic efferent network from the medial septal nucleus to the hippocampus plays an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP), which induces acetylcholine (Ach) synthesis in the medial septal nuclei of an explant culture system, was purified from the soluble fraction of postnatal rat hippocampus. HCNP is processed from the N-terminal region of a 186-amino acid, 21-kDa HCNP precursor protein, also known as Raf kinase inhibitory protein and phosphatidylethanolamine-binding protein 1. Here, we confirmed direct reduction of Ach release in the hippocampus of freely moving HCNP-pp knockout mice under an arousal state by the microdialysis method. The levels of vesicular acetylcholine transporter were also decreased in the hippocampus of these mice in comparison with those in control mice, suggesting there was decreased incorporation of Ach into the synaptic vesicle. These results potently indicate that HCNP may be a cholinergic regulator in the septo-hippocampal network.

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Topics: Cholinergic (59%), Vesicular acetylcholine transporter (58%), Medial septal nucleus (57%) ... read more

Open accessPosted ContentDOI: 10.1101/2021.07.19.452502
Jacopo Agrimi1, Jacopo Agrimi2, Danilo Menicucci3, Marco Laurino4  +10 moreInstitutions (7)
20 Jul 2021-bioRxiv
Abstract: Brain modulation of myocardial activity via the autonomic nervous system is increasingly well characterized. Conversely, how primary alterations in cardiac function, such as an intrinsic increase in heart rate or contractility, reverberate on brain signaling/adaptive behaviors - in a bottom-up modality - remains largely unclear. Mice with cardiac-selective overexpression of adenylyl cyclase type 8 (TGAC8) display increased heart rate and reduced heart rhythm complexity associated with a nearly abolished response to external sympathetic inputs. Here, we tested whether chronically elevated intrinsic cardiac performance alters the heart-brain informational flow, affecting brain signaling and, thus, behavior. To this end, we employed dual lead telemetry for simultaneous recording of EEG and EKG time series in awake, freely behaving TGAC8 mice and wild-type (WT) littermates. We recorded EEG and EKG signals, while monitoring mouse behavior with established tests. Using heart rate variability (HRV) in vivo and isolated atria response to sympathomimetic agents, we first confirmed that the TGAC8 murine heart evades autonomic control. The EEG analysis revealed a substantial drop in theta-2 (4-7 Hz) activity in these transgenic mice. Next, we traced the informational flow between EKG and EEG in the theta-2 frequency band via the Granger causality statistical approach and we found a substantial decrement in the extent of heart/brain bidirectional communication. Finally, TGAC8 mice displayed heightened locomotor activity in terms of behavior, with higher total time mobile, distance traveled, and movement speed while freezing behavior was reduced. Increased locomotion correlated negatively with theta-2 waves count and amplitude. Our study shows that cardiac-born persistent sympathetic stress disrupts the information flow between the heart and brain while influencing central physiological patterns, such as theta activity that controls locomotion. Thus, cardiac-initiated disorders, such as persistently elevated cardiac performance that escapes autonomic control, are penetrant enough to alter brain functions and, thus, primary adaptive behavioral responses.

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Topics: Heart rate variability (56%), Autonomic nervous system (55%), Heart rate (53%) ... read more

Open accessJournal ArticleDOI: 10.1109/ACCESS.2021.3097774
Ting Huang1, Hsien-Ming Ding2, Yi-Li Tseng3Institutions (3)
01 Jan 2021-IEEE Access
Abstract: Phase-amplitude coupling (PAC) is a well-established concept for evaluating the strength of memory coding within brain regions, and has been shown to possess the characteristic of presenting memory mechanisms. It has been demonstrated that oscillations of theta and gamma brain waves can represent the neural coding structure of memory retrieval. However, most previous studies have presented PAC-related memory mechanisms with visual modalities, and little is known about the influence of auditory stimuli. In this study, 18 participants were recruited and 36-channels electroencephalography (EEG) signals were recorded while they were performing an $n$ -back auditory working memory task. There were three experimental conditions with different levels of working memory load. Event-related phase-amplitude coupling (ERPAC) with the advantage of better temporal resolution was used to evaluate the coupling phenomenon from the reconstructed dipole brain sources. We primarily focused on independent components from the frontal and parietal regions, which were reported to be related to memory mechanisms. The results suggest that significant ERPAC was observed in both the frontal and parietal regions. In addition to the coupling between theta (4-7 Hz) and low gamma (30-40 Hz) frequency bands, pronounced high beta oscillations (20-30 Hz) were also observed to be modulated by the phases of theta oscillations. These findings suggest the existence of phase-amplitude coupling in the neocortex during auditory working memory, and provide a highly resolved timeline to evaluate brain dynamics. In addition, the ERPAC results also support the involvement of theta-gamma and theta-beta neural coding mechanisms in cognitive and memory tasks. Collectively, these findings demonstrate the existence of ERPAC within the frontal and parietal regions during an auditory working memory task using complex chords as stimuli, and prompt the use of complex stimuli in studies that are closer to the real-life applications of cognitive evaluations, mental treatments, and brain-computer interfaces.

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Topics: Working memory (66%), Encoding (memory) (55%), Electroencephalography (51%) ... read more


201 results found

Journal ArticleDOI: 10.1016/0006-8993(71)90358-1
John O'Keefe1, Jonathan O. Dostrovsky1Institutions (1)
12 Nov 1971-Brain Research
Abstract: Rats with hippocampal damage are reported to be hyperactive in novel environments, 'perseverative' and resistant to extinction on tasks that they have learned, heedless of drastic changes in their environment, and poor at spatial tasks such as mazes and tasks which require the alteration of responses on successive trials 2,4. These deficits could be due to the loss of the neural system which provides the animal with a cognitive, or spatial, map 5 of its environment. Our preliminary observations on the behaviour of hippocampal units in the freely moving rat provide support for this theory of hippocampal function. Our technique is a modification of one previously used in the spinal cord s and the medulla 1. A small lightweight microdrive which carries up to 8 glass-insulated platinum-plated tungsten microelectrodes is permanently fixed to the rat's skull. Set screws on the manipulator allow any electrode or combination of electrodes to be moved independently of the others. Maximum rejection of muscle and movement artefacts is obtained by feeding the signals from two adjacent microelectrodes into a high input impedance differential FET preamplifier mounted directly on the microdrive. From there, the signal passes through flexible, lightly screened wires to standard recording equipment. In early experiments, two electrodes were glued side by side, one tip 0.5 mm in front of the other, and the pair driven down through the hippocampus together. More recently, satisfactory recordings have been obtained by manipulating one electrode into place in the cortical white matter and fixing it there to serve as a reference for each of the other electrodes in turn. With either method, a constant check was kept on which of the two electrodes carried the unit being studied. For implantation, the rat was anaesthetized with Equithesin and held in a stereotaxic instrument. The microdrive assembly was fixed to its skull with dental cement in such a way that the tips of the electrodes passed through a hole drilled in the skull and rested in the upper layers of the cortex. A day or two later, the rat, fully recovered from the anaesthetic, was placed on the recording stand and the first electrode or pair of electrodes moved down through the cortex and dorsal hippocampus in search of units. The recording stand was a 24 cm × 36 cm raised platform, surrounded on three sides by a white plastic curtain. The fourth side was open, giving the rat a view of the laboratory. Unit activity was monitored during spontaneous behaviours such as walking, eating, drinking, grooming, and sleeping, and during elicited behaviours such as orienting, sniffing at cotton wool or various odours, biting at a polyethylene tube, and in some instances, bar-pressing for food. Responses to simple auditory (clicks, whistles, scratching noises), visual (moving light, hand, black and white striped board), olfactory (various odours, rat faeces), and tactile (touch and pressure over the body surface) stimuli were also tested. All units reported on were studied for at least 15 min and most for more than 30 min.

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Topics: Spatial view cells (52%)

4,957 Citations

Open accessJournal ArticleDOI: 10.1126/SCIENCE.1099745
György Buzsáki1, Andreas Draguhn2Institutions (2)
25 Jun 2004-Science
Abstract: Clocks tick, bridges and skyscrapers vibrate, neuronal networks oscillate. Are neuronal oscillations an inevitable by-product, similar to bridge vibrations, or an essential part of the brain’s design? Mammalian cortical neurons form behavior-dependent oscillating networks of various sizes, which span five orders of magnitude in frequency. These oscillations are phylogenetically preserved, suggesting that they are functionally relevant. Recent findings indicate that network oscillations bias input selection, temporally link neurons into assemblies, and facilitate synaptic plasticity, mechanisms that cooperatively support temporal representation and long-term consolidation of information.

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Topics: Neural oscillation (55%)

4,829 Citations

Journal ArticleDOI: 10.1126/SCIENCE.275.5297.213
10 Jan 1997-Science
Abstract: Activity-driven modifications in synaptic connections between neurons in the neocortex may occur during development and learning In dual whole-cell voltage recordings from pyramidal neurons, the coincidence of postsynaptic action potentials (APs) and unitary excitatory postsynaptic potentials (EPSPs) was found to induce changes in EPSPs Their average amplitudes were differentially up- or down-regulated, depending on the precise timing of postsynaptic APs relative to EPSPs These observations suggest that APs propagating back into dendrites serve to modify single active synaptic connections, depending on the pattern of electrical activity in the pre- and postsynaptic neurons

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3,425 Citations

Tamás F. Freund1, György Buzsáki2Institutions (2)
07 Dec 1998-Hippocampus
Topics: Basket cell (61%), Hippocampus (58%)

3,234 Citations

Journal ArticleDOI: 10.1038/NATURE03721
Torkel Hafting1, Marianne Fyhn1, Sturla Molden2, Sturla Molden1  +2 moreInstitutions (2)
11 Aug 2005-Nature
Abstract: The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in cortical microcircuits is poorly understood. Here we show that the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the 'grid cell', which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.

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Topics: Place cell (54%), Head direction cells (54%), Postrhinal cortex (52%) ... read more

2,993 Citations

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