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

Núñez, Ángel; Buño, Washington

doi:10.3389/fncel.2021.649262

Cited by 107 publications

(74 citation statements)

References 194 publications

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“…In the current study, we showed that the Ach concentration is also reduced in the hippocampus of HCNP-pp KO mice compared with Control mice. Based on our data and previous reports, there is a possibility that the reduction of theta power in HCNP-pp KO mice might be mediated through diminished Ach in the septo-hippocampal formation, which can reduce the activity of GABAergic neurons in the MSN 19 , 20 .…”

Section: Discussionsupporting

confidence: 75%

“…Additionally, the theta activity in CA1 of the hippocampus was reduced in HCNP-pp KO mice 18 . This electrophysiological data suggest that HCNP and/or HCNP-pp is involved in generation of theta oscillations in the hippocampus, which entrains the theta oscillation of the MSN via enhanced ACh release in the medial septum and the enhanced release of ACh in the CA1 stratum oriens 19 , 20 . However, we were unable to demonstrate reduction of Ach release in the hippocampus of those mice, and alteration of cholinergic neurons in the MSN of those mice.…”

Section: Introductionmentioning

confidence: 73%

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Reduction of acetylcholine in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice

Kondo-Takuma

Mizuno

Tsuda

et al. 2021

Sci Rep

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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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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 73%

Reduction of acetylcholine in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice

Kondo-Takuma

Mizuno

Tsuda

et al. 2021

Sci Rep

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“…To assess the physiological relevance of the altered heart-brain communication, we evaluated possible behavioral adaptations in TGAC8s. In rodents, theta rhythms have been linked to locomotor activity because it plays a pivotal role in controlling initiation of the movement 49 and regulating locomotion speed 50,27,51 . Bellesi and coworkers reported that reduced EEG theta power, expressed in the frontal and parietal cortical areas of rats, increased their motor activity, especially when EEG changes were more prominent 52 .…”

Section: Discussionmentioning

confidence: 99%

Cardiac adenylyl cyclase type 8 overexpression increases locomotor activity in mice by modulating EEG-gamma oscillations

Agrimi

Menicucci

Laurino

et al. 2021

Preprint

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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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“…The cholinergic modulation of theta rhythm is well known for decades. Numerous studies have demonstrated that acetylcholine, cholinesterase inhibitors, and cholinergic agonists can induce hippocampal theta oscillation while antagonists block it (reviewed by Nuñez and Buño, 2021 ). Cholinergic induction of theta is largely mediated by the activation of M 1 mAChRs in hippocampal pyramidal neurons ( Ovsepian et al, 2004 ), although nAChRs may also play a role through the basal forebrain cholinergic projections to hippocampal interneurons ( Griguoli et al, 2010 ).…”

Section: Neuromodulationmentioning

confidence: 99%

Neuromodulation of Hippocampal-Prefrontal Cortical Synaptic Plasticity and Functional Connectivity: Implications for Neuropsychiatric Disorders

Ruggiero

Rossignoli

Marques

et al. 2021

Front. Cell. Neurosci.

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

Cited by 107 publications

References 194 publications

Reduction of acetylcholine in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice

Reduction of acetylcholine in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice

Cardiac adenylyl cyclase type 8 overexpression increases locomotor activity in mice by modulating EEG-gamma oscillations

Neuromodulation of Hippocampal-Prefrontal Cortical Synaptic Plasticity and Functional Connectivity: Implications for Neuropsychiatric Disorders

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