Prefrontal-hippocampal coupling by theta rhythm and by 2-5 Hz oscillation in the delta band: The role of the nucleus reuniens of the thalamus.
- Authors
- Roy, Alexis; Svensson, Frans Pettersson; Mazeh, Amna; Kocsis, Bernat
- Year
- 2017
- Journal
- Brain structure & function
- PMID
- 28210848
- DOI
- 10.1007/s00429-017-1374-6
- PMCID
- PMC5542875
Rhythmic synchronizations of hippocampus (HC) and prefrontal cortex (PFC) at theta frequencies (4-8 Hz) are thought to mediate key cognitive functions, and disruptions of HC-PFC coupling were implicated in psychiatric diseases. Theta coupling is thought to represent a HC-to-PFC drive transmitted via the well-described unidirectional HC projection to PFC. In comparison, communication in the PFC-to-HC direction is less understood, partly because no known direct anatomical connection exists. Two recent findings, i.e., reciprocal projections between the thalamic nucleus reuniens (nRE) with both PFC and HC and a unique 2-5 Hz rhythm reported in the PFC, indicate, however, that a second low-frequency oscillation may provide a synchronizing signal from PFC to HC via nRE. Thus, in this study, we recorded local field potentials in the PFC, HC, and nRE to investigate the role of nRE in PFC-HC coupling established by the two low-frequency oscillations. Using urethane-anesthetized rats and stimulation of pontine reticular formation to experimentally control the parameters of both forebrain rhythms, we found that theta and 2-5 Hz rhythm were dominant in HC and PFC, respectively, but were present and correlated in all three signals. Removal of nRE influence, either statistically (by partialization of PFC-HC correlation when controlling for the nRE signal) or pharmacologically (by lidocaine microinjection in nRE), resulted in decreased coherence between the PFC and HC 2-5-Hz oscillations, but had minimal effect on theta coupling. This study proposes a novel thalamo-cortical network by which PFC-to-HC coupling occurs via a 2-5 Hz oscillation and is mediated through the nRe.
Spontaneous alternation between wide-band delta activity and simultaneous 2–5 Hz and theta oscillations in urethane anesthetized ratsA. Example of time-frequency plots represents alternating wide-band delta activity and two oscillations at 1.9 and 4.6 Hz in PFC, HC and nRE. B and C. Sample LFP recordings on a faster time scale showing large amplitude irregular activity (B) and rhythmic activity (C). D and E. Power spectra of 75 s PFC and HC signals exhibiting wide-band spectral components (D) and sharp peaks (E), both within the delta range (power spectra overlaid for different signals were autoscaled to the largest peak). Voltage calibration in B and C: 0.5mV.
2–5 Hz oscillation elicited in PFC simultaneously with HC theta by RPO stimulationA. Time-frequency plot demonstrating PFC, HC and nRE oscillations elicited by RPO stimulation at different intensities (between 0.08 and 0.33 mA). Note 2–5 Hz and theta expressed to different extent in different signals, e.g. 2–5 Hz in PFC, theta in HC, and both in nRE at 0.15 mA, and theta only in all signals at 0.33 mA. B. Sample LFP recordings of PFC 2–5 Hz oscillation and HC theta interrupting ongoing large amplitude irregular activity at the onset of RPO stimulation at low intensity (0.15 mA). (C). High intensity (0.33 mA) RPO stimulation induced theta in all 3 signals. D–F. Power spectra of PFC (D), HC (E), and nRE (F) LFP signals shown in B and C during low (blue) and high intensity (red) RPO stimulation. Note different scales for D-F. Voltage calibration in B and C: 0.5mV.
Changes in frequency and power of 2–5 Hz and theta oscillations elicited by stimulation of RPO at five different stimulus intensitiesA–C. Sample power spectra of PFC (A), HC (B), and nRE (C) signals during RPO stimulation at different intensities. Colors represent increasing stimulus intensities. Inserts in A and B show power spectra in the frequency bands of the non-dominant components, i.e. 4–9 Hz in PFC and 1–4 Hz in HC, on a on a larger scale. Note faster and larger theta and faster and lower 2–5 Hz oscillations at higher intensities (arrows). D. Group averages of the frequency of 2–5 Hz and theta oscillations elicited by RPO stimulation at different intensities. E-F. Group averages of spectral power at theta (E) and at 2–5 Hz (F) in PFC, HC, and nRE. Peak frequencies for theta and 2–5 Hz were identified on HC and PFC spectra, respectively, and spectral power at these frequencies, on the condition of the presence of local maxima (however small), were averaged for the three signals. In D–F, continuous lines represent averages of all rats (n=15), dashed lines represent experiments with significant PFC-HC correlation (n=7 for theta and n=13 for 2–5 Hz). Error bars represent standard error of the mean.
Relationship between PFC, HC, and nRE rhythmic LFPs at 2–5 Hz and theta frequenciesA. Scatterplot of peak power at 2–5 Hz (blue) and theta (red) frequencies in PFC and HC (all stimulation episodes, n=537 in 15 rats). B. Scatterplot of peak power in PFC vs. nRE at 2–5 Hz (blue) and HC vs. nRE at theta (red) frequencies. C. Pairwise correlation of 2–5 Hz and theta oscillations between different structures (mean±S.E.M.; correlations calculated using all data points in all rats). D. Pairwaise correlations in individual experiments (numbers show overlapping experiments with r=0). E. Pairwise correlation of 2–5 Hz and theta oscillations between different structures (mean±S.E.M.; correlations calculated separately for each rat, and averaged over the group of n=15, after non-significant correlations set to =0). F. Correlation structure of RPO induced oscillations between PFC, HC, and nRE. Thickness of lines is proportional to correlations at 2–5 Hz (blue) and theta (red) frequencies. In A and B, LFP voltages were normalized for each experiment and expressed in arbitrary units (between 0 and 1).
Partialization of significant PFC-HC correlations by nREA. Group averages of pairwise correlation of 2–5 Hz and theta oscillations between PFC, HC, and nRE, only including experiments with significant PFC-HC correlations at both frequencies (n=7). B. Correlation structure of RPO induced oscillations between PFC, HC, and nRE for this group. C and D. PFC-HC correlations and PFC-HC/nRE partial correlation: group averages (C), and the effect of partialization in individual experiments (ns: partial correlation not significantly different from zero) (D). E. Pairwise partial correlations after controlling for the third signal. Note complete elimination of PFC-HC 2–5 Hz correlation and HC-nRE theta correlation. Note also relatively high and equal residual PFC-nRE correlations at the 2 frequencies (theta: 0.42; 2–5 Hz: 0.44). In B and E thickness of lines is proportional to peak correlations at 2–5 Hz (blue) and theta (red) frequencies.
Effect of nRE inactivation on HC-PFC delta and theta coherenceA. Coherence spectra of all pairwise combinations between 2 PFC and 4 HC recordings in the delta (0–4 Hz, left) and theta (4–9 Hz) frequency ranges before (blue) and after (red) microinjection of 0.1 mg (1 uL, 0.374 uL/min) lidocaine in the nRE. Sample coherence spectra from a representative experiment are shown during low (left) and high (right) RPO stimulation. B. Pre- and post-lidocaine peak coherence for pairs of PFC-vHC and PFC-dHC recordings. Individual peaks are plotted as dots (delta) or rhomboids (theta); open symbols mark experiments with no significant drug effect. Each bar represents the mean of peak coherence values in one condition, for all rats. C. The change in peak delta and theta coherence after lidocaine injection, averaged over all PFC-HC pairs (n= 32 combinations in 4 rats). D. Group averages of coherence peak values in pre- and post-lidocaine recordings. Pharmacological inactivation of the nRE had minimal effect on coherence between the PFC and HC for theta oscillations (p = 0.19), whereas significant decreased the coherence for oscillation in the delta range (p <0.001).
Possible models of HC-PFC oscillatory coupling at two frequenciesA. Model summarizing the known anatomical connections and their selective involvement, as shown in this study, in conveying 2–5 Hz and theta oscillatory signal between PFC and HC. First, our data are in agreement with the direct HC-to-PFC pathway carrying theta synchronizing signal. Second, synchronization at 2–5 Hz was found to involve the nRE and could use reciprocal nRE connections with both PFC and HC. Third, several other structures, not recorded in this study, also have reciprocal connections with PFC and HC and could be the origin of residual correlations, including the amygdala (AMY), supramammillary nucleus (SUM), entorhinal cortex (EC), medial septum (MS), and ventral tegmental area (VTA). B. Functional model in which the 2–5 Hz oscillation is generated by a thalamo-cortical (nRE-PFC) network. The primary input to this network receiving HC theta influence is the PFC. A secondary input for HC theta directed to this network is available through the nRE. The common output of the network through which 2–5 Hz synchronizing signal can be sent to the HC is the nRE.
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| An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits. | Cheung H et al. | — | 2024 | → |
| Neural circuits for the adaptive regulation of fear and extinction memory. | Plas SL et al. | — | 2024 | → |
| Coupling between the prelimbic cortex, nucleus reuniens, and hippocampus during NREM sleep remains stable under cognitive and homeostatic demands. | Bozic I et al. | — | 2023 | → |
| Development of network oscillations through adolescence in male and female rats. | Sibilska S et al. | — | 2023 | → |
| Dopamine D4 Receptor Agonist Drastically Increases Delta Activity in the Thalamic Nucleus Reuniens: Potential Role in Communication between Prefrontal Cortex and Hippocampus. | Kuang J et al. | — | 2023 | → |
| Hippocampal non-theta state: The "Janus face" of information processing. | Mysin I et al. | — | 2023 | → |
| Paroxysmal slow-wave discharges in a model of absence seizure are coupled to gamma oscillations in the thalamocortical and limbic systems. | Ajaz R et al. | — | 2023 | → |
| Predicting Alcohol-Related Memory Problems in Older Adults: A Machine Learning Study with Multi-Domain Features. | Kamarajan C et al. | — | 2023 | → |
| Respiration organizes gamma synchrony in the prefronto-thalamic network. | Basha D et al. | — | 2023 | → |
| Task-specific oscillatory synchronization of prefrontal cortex, nucleus reuniens, and hippocampus during working memory. | de Mooij-van Malsen JG et al. | — | 2023 | → |
| Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear. | Totty MS et al. | — | 2023 | → |
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| Breaking Down a Rhythm: Dissecting the Mechanisms Underlying Task-Related Neural Oscillations. | Ibarra-Lecue I et al. | — | 2022 | → |
| Differential Effect of Dopamine D4 Receptor Activation on Low-Frequency Oscillations in the Prefrontal Cortex and Hippocampus May Bias the Bidirectional Prefrontal-Hippocampal Coupling. | Thörn CW et al. | — | 2022 | → |
| Echolocation-related reversal of information flow in a cortical vocalization network. | García-Rosales F et al. | — | 2022 | → |
| Hippocampal-prefrontal interactions during spatial decision-making. | Tavares LCS et al. | — | 2022 | → |
| Pathways for Memory, Cognition and Emotional Context: Hippocampal, Subgenual Area 25, and Amygdalar Axons Show Unique Interactions in the Primate Thalamic Reuniens Nucleus. | Joyce MKP et al. | — | 2022 | → |
| Prefrontal projections to the nucleus reuniens signal behavioral relevance of stimuli during associative learning. | Yu X et al. | — | 2022 | → |
| Replicable patterns of causal information flow between hippocampus and prefrontal cortex during spatial navigation and spatial-verbal memory formation. | Das A et al. | — | 2022 | → |
| The effect of ketamine on delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb. | Staszelis A et al. | — | 2022 | → |
| The role of aberrant neural oscillations in the hippocampal-medial prefrontal cortex circuit in neurodevelopmental and neurological disorders. | Shing N et al. | — | 2022 | → |
| Asymmetric Frequency-Specific Feedforward and Feedback Information Flow between Hippocampus and Prefrontal Cortex during Verbal Memory Encoding and Recall. | Das A et al. | — | 2021 | → |
| Beta2 Oscillations in Hippocampal-Cortical Circuits During Novelty Detection. | França ASC et al. | — | 2021 | → |
| Calretinin and calbindin architecture of the midline thalamus associated with prefrontal-hippocampal circuitry. | Viena TD et al. | — | 2021 | → |
| Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats. | Mofleh R et al. | — | 2021 | → |
| Midline Thalamic Damage Associated with Alcohol-Use Disorders: Disruption of Distinct Thalamocortical Pathways and Function. | Savage LM et al. | — | 2021 | → |
| Neuromodulation of Hippocampal-Prefrontal Cortical Synaptic Plasticity and Functional Connectivity: Implications for Neuropsychiatric Disorders. | Ruggiero RN et al. | — | 2021 | → |
| Neuronal oscillations and the mouse prefrontal cortex. | Jung F et al. | — | 2021 | → |
| Nucleus Reuniens Lesion and Antidepressant Treatment Prevent Hippocampal Neurostructural Alterations Induced by Chronic Mild Stress in Male Rats. | Kafetzopoulos V et al. | — | 2021 | → |
| Nucleus reuniens of the thalamus controls fear memory reconsolidation. | Troyner F et al. | — | 2021 | → |
| Plasticity in Prefrontal Cortex Induced by Coordinated Synaptic Transmission Arising from Reuniens/Rhomboid Nuclei and Hippocampus. | Banks PJ et al. | — | 2021 | → |
| Respiratory coupling between prefrontal cortex and hippocampus of rats anaesthetized with urethane in theta and non-theta states. | Mofleh R et al. | — | 2021 | → |
| The reuniens and rhomboid nuclei of the thalamus: A crossroads for cognition-relevant information processing? | Cassel JC et al. | — | 2021 | → |
| Afferent connections of the thalamic nucleus reuniens in the mouse. | Scheel N et al. | — | 2020 | → |
| Calretinin and calbindin architecture of the midline thalamus associated with prefrontal-hippocampal circuitry | Viena TD et al. | — | 2020 | — |
| Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo. | Lopes-Aguiar C et al. | — | 2020 | → |
| Neurophysiological alterations in the nucleus reuniens of a mouse model of Alzheimer's disease. | Walsh DA et al. | — | 2020 | → |
| Perspective on the Multiple Pathways to Changing Brain States. | Tantirigama MLS et al. | — | 2020 | → |
| Single-day Postnatal Alcohol Exposure Induces Apoptotic Cell Death and Causes long-term Neuron Loss in Rodent Thalamic Nucleus Reuniens. | Gursky ZH et al. | — | 2020 | → |
| Thalamic nucleus reuniens regulates fear memory destabilization upon retrieval. | Troyner F et al. | — | 2020 | → |
| The anterior thalamic nuclei and nucleus reuniens: So similar but so different. | Mathiasen ML et al. | — | 2020 | → |
| The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties. | Chao OY et al. | — | 2020 | → |
| The thalamic midline nucleus reuniens: potential relevance for schizophrenia and epilepsy. | Dolleman-van der Weel MJ et al. | — | 2020 | → |
| ACC Theta Improves Hippocampal Contextual Processing during Remote Recall. | Wirt RA et al. | — | 2019 | → |
| D-type potassium channels normalize action potential firing between dorsal and ventral CA1 neurons of the mouse hippocampus. | Ordemann GJ et al. | — | 2019 | → |
| Glucocorticoid enhancement of recognition memory via basolateral amygdala-driven facilitation of prelimbic cortex interactions. | Barsegyan A et al. | — | 2019 | → |
| Inferring the direction of rhythmic neural transmission via inter-regional phase-amplitude coupling (ir-PAC). | Nandi B et al. | — | 2019 | → |
| The nucleus reuniens of the thalamus sits at the nexus of a hippocampus and medial prefrontal cortex circuit enabling memory and behavior. | Dolleman-van der Weel MJ et al. | — | 2019 | → |
| The Reuniens Nucleus of the Thalamus Has an Essential Role in Coordinating Slow-Wave Activity between Neocortex and Hippocampus. | Hauer BE et al. | — | 2019 | → |
| Ventral midline thalamus lesion prevents persistence of new (learning-triggered) hippocampal spines, delayed neocortical spinogenesis, and spatial memory durability. | Klein MM et al. | — | 2019 | → |
| Dendrites of the dorsal and ventral hippocampal CA1 pyramidal neurons of singly housed female rats exhibit lamina-specific growths and retractions during adolescence that are responsive to pair housing. | Chen YW et al. | — | 2018 | → |
| Inactivation of nucleus reuniens impairs spatial working memory and behavioral flexibility in the rat. | Viena TD et al. | — | 2018 | → |
| Input Convergence, Synaptic Plasticity and Functional Coupling Across Hippocampal-Prefrontal-Thalamic Circuits. | Bueno-Junior LS et al. | — | 2018 | → |
| Nasal respiration entrains delta-frequency oscillations in the prefrontal cortex and hippocampus of rodents. | Lockmann ALV et al. | — | 2018 | → |
| Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long-term maintenance during consolidation. | Troyner F et al. | — | 2018 | → |
| Parallel detection of theta and respiration-coupled oscillations throughout the mouse brain. | Tort ABL et al. | — | 2018 | → |
| Prefrontal projections to the thalamic nucleus reuniens mediate fear extinction. | Ramanathan KR et al. | — | 2018 | → |
| Respiration-coupled rhythms in prefrontal cortex: beyond if, to when, how, and why. | Kocsis B et al. | — | 2018 | → |
| Respiration-Entrained Brain Rhythms Are Global but Often Overlooked. | Tort ABL et al. | — | 2018 | → |
| Subunit-specific NMDAR antagonism dissociates schizophrenia subtype-relevant oscillopathies associated with frontal hypofunction and hippocampal hyperfunction. | Pittman-Polletta B et al. | — | 2018 | → |
| Taming the oscillatory zoo in the hippocampus and neo-cortex: a review of the commentary of Lockmann and Tort on Roy et al. | Bagur S et al. | — | 2018 | → |
| The activity of thalamic nucleus reuniens is critical for memory retrieval, but not essential for the early phase of "off-line" consolidation. | Mei H et al. | — | 2018 | → |
| Ventral Midline Thalamus Is Necessary for Hippocampal Place Field Stability and Cell Firing Modulation. | Cholvin T et al. | — | 2018 | → |
| Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation. | Kim B et al. | — | 2017 | → |
| The claustrum: Considerations regarding its anatomy, functions and a programme for research. | Dillingham CM et al. | — | 2017 | → |