Pacemaker Neurons for the Theta Rhythm and Their Synchronization in the Septohippocampal Reciprocal Loop

2002 ◽  
Vol 87 (2) ◽  
pp. 889-900 ◽  
Author(s):  
Xiao-Jing Wang
Keyword(s):  
Theta Rhythm ◽  
Medial Septum ◽  
Theta Oscillations ◽  
Biophysical Modeling ◽  
Cellular Mechanisms ◽  
Brain Rhythm ◽  
Network Simulations ◽  
Low Threshold ◽  
Inhibitory Circuit ◽  
Hippocampal Theta

Hippocampal theta (4–10 Hz) oscillation represents a well-known brain rhythm implicated in spatial cognition and memory processes. Its cellular mechanisms remain a matter of debate, and previous computational work has focused mostly on mechanisms intrinsic to the hippocampus. On the other hand, experimental data indicate that GABAergic cells in the medial septum play a pacemaker role for the theta rhythm. We have used biophysical modeling to address two major questions raised by the septal pacemaker hypothesis: what is the ion channel mechanism for the single-cell pacemaker behavior and how do these cells become synchronized? Our model predicts that theta oscillations of septal GABAergic cells depend critically on a low-threshold, slowly inactivating potassium current. Network simulations show that theta oscillations are not coherent in an isolated population of pacemaker cells. Robust synchronization emerges with the addition of a second GABAergic cell population. Such a reciprocally inhibitory circuit can be realized by the hippocampo-septal feedback loop.

scholarly journals A distinctive subpopulation of medial septal slow-firing neurons promote hippocampal activation and theta oscillations

2011 ◽  
Vol 106 (5) ◽  
pp. 2749-2763 ◽  
Author(s):  
Hao Zhang ◽  
Shih-Chieh Lin ◽  
Miguel A. L. Nicolelis
Keyword(s):  
Medial Septum ◽  
Theta Oscillations ◽  
Short Term ◽  
Neuronal Ensembles ◽  
Gamma Range ◽  
Diagonal Band ◽  
Hippocampal Activity ◽  
Diagonal Band Of Broca ◽  
Hippocampal Theta ◽  
Relationship Of

The medial septum-vertical limb of the diagonal band of Broca (MSvDB) is important for normal hippocampal functions and theta oscillations. Although many previous studies have focused on understanding how MSVDB neurons fire rhythmic bursts to pace hippocampal theta oscillations, a significant portion of MSVDB neurons are slow-firing and thus do not pace theta oscillations. The function of these MSVDB neurons, especially their role in modulating hippocampal activity, remains unknown. We recorded MSVDB neuronal ensembles in behaving rats, and identified a distinct physiologically homogeneous subpopulation of slow-firing neurons (overall firing <4 Hz) that shared three features: 1) much higher firing rate during rapid eye movement sleep than during slow-wave (SW) sleep; 2) temporary activation associated with transient arousals during SW sleep; 3) brief responses (latency 15∼30 ms) to auditory stimuli. Analysis of the fine temporal relationship of their spiking and theta oscillations showed that unlike the theta-pacing neurons, the firing of these “pro-arousal” neurons follows theta oscillations. However, their activity precedes short-term increases in hippocampal oscillation power in the theta and gamma range lasting for a few seconds. Together, these results suggest that these pro-arousal slow-firing MSvDB neurons may function collectively to promote hippocampal activation.

scholarly journals Shared rhythmic subcortical GABAergic input to the entorhinal cortex and presubiculum

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Tim James Viney ◽  
Minas Salib ◽  
Abhilasha Joshi ◽  
Gunes Unal ◽  
Naomi Berry ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Gamma Oscillations ◽  
Medial Septum ◽  
Theta Oscillations ◽  
Cortical Circuits ◽  
Cellular Mechanisms ◽  
Neuronal Synchrony ◽  
Theta Frequency ◽  
Episodic Memories ◽  
Gabaergic Modulation

Rhythmic theta frequency (~5–12 Hz) oscillations coordinate neuronal synchrony and higher frequency oscillations across the cortex. Spatial navigation and context-dependent episodic memories are represented in several interconnected regions including the hippocampal and entorhinal cortices, but the cellular mechanisms for their dynamic coupling remain to be defined. Using monosynaptically-restricted retrograde viral tracing in mice, we identified a subcortical GABAergic input from the medial septum that terminated in the entorhinal cortex, with collaterals innervating the dorsal presubiculum. Extracellularly recording and labeling GABAergic entorhinal-projecting neurons in awake behaving mice show that these subcortical neurons, named orchid cells, fire in long rhythmic bursts during immobility and locomotion. Orchid cells discharge near the peak of hippocampal and entorhinal theta oscillations, couple to entorhinal gamma oscillations, and target subpopulations of extra-hippocampal GABAergic interneurons. Thus, orchid cells are a specialized source of rhythmic subcortical GABAergic modulation of ‘upstream’ and ‘downstream’ cortico-cortical circuits involved in mnemonic functions.

scholarly journals Interconnection and synchronization of neuronal populations in the mouse medial septum/diagonal band of Broca

2015 ◽  
Vol 113 (3) ◽  
pp. 971-980 ◽  
Author(s):  
Richardson N. Leão ◽  
Zé H. Targino ◽  
Luis V. Colom ◽  
André Fisahn
Keyword(s):  
Action Potentials ◽  
Theta Rhythm ◽  
Medial Septum ◽  
Gabaergic Neurons ◽  
Action Potential Firing ◽  
Neuronal Populations ◽  
Diagonal Band ◽  
Potential Firing ◽  
Diagonal Band Of Broca ◽  
Hippocampal Theta

The medial septum/diagonal band of Broca (MS/DBB) is crucial for hippocampal theta rhythm generation (4–12 Hz). However, the mechanisms behind theta rhythmogenesis are still under debate. The MS/DBB consists, in its majority, of three neuronal populations that use acetylcholine, GABA, or glutamate as neurotransmitter. While the firing patterns of septal neurons enable the MS/DBB to generate rhythmic output critical for the generation of the hippocampal theta rhythm, the ability to synchronize these action potentials is dependent on the interconnectivity between the three major MS/DBB neuronal populations, yet little is known about intraseptal connections. Here we assessed the connectivity between pairs of MS/DBB neurons with paired patch-clamp recordings. We found that glutamatergic and GABAergic neurons provide intraseptal connections and produce sizable currents in MS/DBB postsynaptic cells. We also analyzed linear and nonlinear relationships between the action potentials fired by pairs of neurons belonging to various MS/DBB neuronal populations. Our results show that while the synchrony index for action potential firing was significantly higher in pairs of GABAergic neurons, coherence of action potential firing in the theta range was similarly low in all pairs analyzed. Recurrence analysis demonstrated that individual action potentials were more recurrent in cholinergic neurons than in other cell types. Implementing sparse connectivity in a computer model of the MS/DBB network reproduced our experimental data. We conclude that the interplay between the intrinsic membrane properties of different MS/DBB neuronal populations and the connectivity among these populations underlie the ability of the MS/DBB network to critically contribute to hippocampal theta rhythmogenesis.

scholarly journals Lamotrigine Attenuates Neuronal Excitability, Depresses GABA Synaptic Inhibition, and Modulates Theta Rhythms in Rat Hippocampus

2021 ◽  
Author(s):  
Paulina Kazmierska-Grebowska ◽  
Marcin Siwiec ◽  
Joanna Ewa Sowa ◽  
Caban Bartosz ◽  
Tomasz Kowalczyk ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Medial Septum ◽  
Movement Planning ◽  
Theta Oscillations ◽  
Hcn Channels ◽  
Anaesthetized Rats ◽  
Hippocampal Theta

Theta oscillations generated in hippocampal (HPC) and cortical neuronal networks are involved in various aspects of brain function, including sensorimotor integration, movement planning, memory formation and attention. Disruptions of theta rhythms are present in individuals with various disorders, including epilepsy and Alzheimer&rsquo;s disease. Theta rhythm generation involves a specific interplay between cellular (ionic) and network (synaptic) mechanisms. HCN channels are theta modulators, and several medications are known to enhance their activity. We investigated how different doses of lamotrigine (LTG), an HCN channel activator, and antiepileptic and neuroprotective agent, would affect hippocampal theta rhythms in acute HPC slices (in vitro) and anaesthetized rats (in vivo). Whole-cell patch clamp recordings revealed that LTG decreased GABAA-fast transmission in CA3 and CA1 cells, in vitro. In addition, LTG directly depressed CA3 and CA1 pyramidal neuron excitability. These effects were partially blocked by ZD 7288, a selective HCN blocker, and are consistent with decreased excitability associated with antiepileptic actions. Lamotrigine also depressed hippocampal theta oscillations in vitro, also consistent with its neuronal depressant effects. In contrast, it exerted an opposite, enhancing effect, on theta recorded in vivo. The contradictory in vivo and in vitro results indicate that LTG increases ascending theta activating medial septum/entorhinal synaptic inputs that over-power the depressant effects seen in hippocampal neurons. These results provide new insights into LTG actions and indicate an opportunity to develop more precise therapeutics for the treatment of dementias, memory disorders and epilepsy.

Two populations of rhythmically bursting neurons in rat medial septum are revealed by atropine

1989 ◽  
Vol 61 (5) ◽  
pp. 982-993 ◽  
Author(s):  
M. Stewart ◽  
S. E. Fox
Keyword(s):  
Time Course ◽  
Theta Rhythm ◽  
Rhythmic Activity ◽  
Medial Septum ◽  
Hippocampal Theta Rhythm ◽  
Diagonal Band ◽  
Septohippocampal System ◽  
Rhythmic Firing ◽  
Hippocampal Theta ◽  
Resistant Cells

1. Previous findings, such as the sensitivity of the hippocampal theta rhythm to cholinergic manipulation, support a "pacemaker" role for the cholinergic cells of the medial septal nucleus and the vertical limb of the nucleus of the diagonal band (MSN-NDB). To explore the mechanism(s) of action of systemic antimuscarinic drugs in eliminating the theta rhythm, recordings of hippocampal EEG and rhythmic MSN-NDB neurons that fired in phase with the hippocampal theta rhythm were taken during the administration of atropine in urethane-anesthetized rats. 2. Twenty-two of 33 rhythmic MSN-NDB cells continued to burst at the theta rhythm frequency after administration of a dose of atropine (25 mg/kg iv) that was sufficient to eliminate the theta rhythm (atropine-resistant cells). The remaining 11 cells lost their rhythmic firing pattern over the same time course as the loss of the theta rhythm (atropine-sensitive cells). 3. Both types of rhythmic MSN-NDB cells could be antidromically driven from the fimbria/fornix with similar latencies (range, 0.5-4.0 ms). The extracellularly recorded spike waveforms were not useful in predicting the atropine sensitivity of a given cell. Atropine-resistant cells frequently had higher firing rates than atropine-sensitive cells, but there was sufficient overlap of the two groups to make this a poor predictor of sensitivity. 4. Cooling the fimbria/fornix reversibly eliminated the hippocampal theta rhythm, but had no effect on 21/25 rhythmic MSN-NDB cells tested. This indicates that the atropine-sensitive MSN-NDB cells do not depend on the periodic output from the hippocampus for their rhythmic firing. Recordings from pairs of rhythmic MSN-NDB cells during cooling and/or atropine administration showed unchanged phase relations at the theta rhythm frequency. In rats in which the septohippocampal system was exposed by aspirating the overlying brain tissue, direct application of atropine (10 mg/ml) to the septal nuclei reversibly eliminated the hippocampal theta rhythm. 5. The rhythmic cells of the MSN-NDB are apparently composed of at least two distinct types, both of which potentially contribute to the production of the theta rhythm in the hippocampus. Elimination of hippocampal theta rhythm after local septal atropine application suggests that the loss of rhythmic activity in the group of atropine-sensitive septal cells is sufficient for the elimination of the theta rhythm. A model of the septohippocampal connections necessary for the theta rhythm is presented.

scholarly journals Interneuronal mechanisms of hippocampal theta oscillations in a full-scale model of the rodent CA1 circuit

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Marianne J Bezaire ◽  
Ivan Raikov ◽  
Kelly Burk ◽  
Dhrumil Vyas ◽  
Ivan Soltesz
Keyword(s):  
Information Processing ◽  
Theta Rhythm ◽  
Gamma Oscillations ◽  
Full Scale ◽  
Theta Oscillations ◽  
Data Driven ◽  
Scale Model ◽  
Hippocampal Theta Rhythm ◽  
Ca1 Area ◽  
Hippocampal Theta

The hippocampal theta rhythm plays important roles in information processing; however, the mechanisms of its generation are not well understood. We developed a data-driven, supercomputer-based, full-scale (1:1) model of the rodent CA1 area and studied its interneurons during theta oscillations. Theta rhythm with phase-locked gamma oscillations and phase-preferential discharges of distinct interneuronal types spontaneously emerged from the isolated CA1 circuit without rhythmic inputs. Perturbation experiments identified parvalbumin-expressing interneurons and neurogliaform cells, as well as interneuronal diversity itself, as important factors in theta generation. These simulations reveal new insights into the spatiotemporal organization of the CA1 circuit during theta oscillations.

scholarly journals Medial septal GABAergic projection neurons promote object exploration behavior and type 2 theta rhythm

2016 ◽  
Vol 113 (23) ◽  
pp. 6550-6555 ◽  
Author(s):  
Gireesh Gangadharan ◽  
Jonghan Shin ◽  
Seong-Wook Kim ◽  
Angela Kim ◽  
Afshin Paydar ◽  
...  
Keyword(s):  
Open Field ◽  
Theta Rhythm ◽  
Critical Role ◽  
Well Being ◽  
Medial Septum ◽  
Projection Neurons ◽  
Object Exploration ◽  
Exploration Behavior ◽  
Hippocampal Theta

Exploratory drive is one of the most fundamental emotions, of all organisms, that are evoked by novelty stimulation. Exploratory behavior plays a fundamental role in motivation, learning, and well-being of organisms. Diverse exploratory behaviors have been described, although their heterogeneity is not certain because of the lack of solid experimental evidence for their distinction. Here we present results demonstrating that different neural mechanisms underlie different exploratory behaviors. Localized Cav3.1 knockdown in the medial septum (MS) selectively enhanced object exploration, whereas the null mutant (KO) mice showed enhanced-object exploration as well as open-field exploration. In MS knockdown mice, only type 2 hippocampal theta rhythm was enhanced, whereas both type 1 and type 2 theta rhythm were enhanced in KO mice. This selective effect was accompanied by markedly increased excitability of septo-hippocampal GABAergic projection neurons in the MS lacking T-type Ca2+ channels. Furthermore, optogenetic activation of the septo-hippocampal GABAergic pathway in WT mice also selectively enhanced object exploration behavior and type 2 theta rhythm, whereas inhibition of the same pathway decreased the behavior and the rhythm. These findings define object exploration distinguished from open-field exploration and reveal a critical role of T-type Ca2+ channels in the medial septal GABAergic projection neurons in this behavior.

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