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 ◽  
...  

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.

2015 ◽  
Vol 113 (3) ◽  
pp. 971-980 ◽  
Author(s):  
Richardson N. Leão ◽  
Zé H. Targino ◽  
Luis V. Colom ◽  
André Fisahn

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.


1989 ◽  
Vol 61 (5) ◽  
pp. 982-993 ◽  
Author(s):  
M. Stewart ◽  
S. E. Fox

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.


2021 ◽  
Author(s):  
Soraya L.S. Dunn ◽  
Stephen M. Town ◽  
Jennifer K. Bizley ◽  
Daniel Bendor

Theta oscillations are a hallmark of hippocampal activity across mammalian species and play a critical role in many hippocampal models of memory and spatial navigation. To attempt to reconcile the cross-species differences observed in the presence and properties of theta, we recorded hippocampal local field potentials in rats and ferrets during a localisation task designed to vary locomotion and sensory attention. Here we show that theta oscillations occur during locomotion in both the ferret and rat, however during periods of immobility, theta oscillations persisted in the ferret, contrasting starkly with the switch to large irregular activity (LIA) in the rat. Theta during immobility in the ferret was identified as Type 2 theta due to its sensitivity to atropine and was modulated by behavioural state, with the strongest theta observed during reward epochs. These results demonstrate that even under similar behavioural conditions, there is a variable relationship between theta and behavioural state across different species.


2002 ◽  
Vol 87 (2) ◽  
pp. 889-900 ◽  
Author(s):  
Xiao-Jing Wang

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.


2018 ◽  
Vol 20 (3) ◽  
pp. 99-110
Author(s):  
Na Zhang ◽  
Jingjing Li ◽  
Xing Bu ◽  
Zhenxing Gong ◽  
Gilal Faheem Gul

Sign in / Sign up

Export Citation Format

Share Document