scholarly journals The lateral septum as a regulator of hippocampal theta oscillations and defensive behavior in rats

2015 ◽  
Vol 113 (6) ◽  
pp. 1831-1841 ◽  
Author(s):  
San-San A. Chee ◽  
Janet L. Menard ◽  
Hans C. Dringenberg

Hippocampal theta oscillations are linked to various processes, including locomotion, learning and memory, and defense and affect. The lateral septum (LS) has been implicated in the generation of the hippocampal theta rhythm, but its precise role in this process is not well understood. Here, we investigated the effects of direct pharmacological inhibition or disinhibition of the dorsal LS (dLS) on the frequency of hippocampal theta activity elicited by stimulation of the reticular formation in urethane-anesthetized rats. We found that bilateral infusions of the GABAA receptor agonist muscimol into the dLS significantly increased theta frequency. Strikingly, intra-dLS infusions of the GABAA receptor antagonist GABAzine largely abolished reticularly elicited theta activity. We also locally injected these same compounds into the medial septum (MS) to test for neuroanatomical specificity. In contrast to the effects seen in the dLS, intra-MS infusions of muscimol had no effect on theta frequency, whereas intra-MS infusions of GABAzine increased theta frequency. Given the hypothesized role of hippocampal theta in behavioral defense, we also examined the effects of intra-dLS application of muscimol in two models of anxiety, the elevated plus maze and the novelty-induced suppression of feeding paradigm; both tests revealed clear, anxiolytic-like effects following muscimol infusions. The fact that dLS-muscimol increased theta frequency while also reducing anxiety-like behaviors challenges the influential theta suppression model of anxiolysis, which predicts a slowing of theta with anxiolytic compounds. More importantly, the experiments reveal a novel role of the LS, especially its dorsal aspects, as an important gating mechanism for the expression of theta oscillations in the rodent hippocampus.

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Angus Chadwick ◽  
Mark CW van Rossum ◽  
Matthew F Nolan

Encoding of behavioral episodes as spike sequences during hippocampal theta oscillations provides a neural substrate for computations on events extended across time and space. However, the mechanisms underlying the numerous and diverse experimentally observed properties of theta sequences remain poorly understood. Here we account for theta sequences using a novel model constrained by the septo-hippocampal circuitry. We show that when spontaneously active interneurons integrate spatial signals and theta frequency pacemaker inputs, they generate phase precessing action potentials that can coordinate theta sequences in place cell populations. We reveal novel constraints on sequence generation, predict cellular properties and neural dynamics that characterize sequence compression, identify circuit organization principles for high capacity sequential representation, and show that theta sequences can be used as substrates for association of conditioned stimuli with recent and upcoming events. Our results suggest mechanisms for flexible sequence compression that are suited to associative learning across an animal’s lifespan.


2018 ◽  
Author(s):  
Hyowon Chung ◽  
Kyerl Park ◽  
Hyun Jae Jang ◽  
Michael M Kohl ◽  
Jeehyun Kwag

AbstractAbnormal accumulation of amyloid β oligomers (AβO) is a hallmark of Alzheimer’s disease (AD), which leads to learning and memory deficits. Hippocampal theta oscillations that are critical in spatial navigation, learning and memory are impaired in AD. Since GABAergic interneurons, such as somatostatin-positive (SST+) and parvalbumin-positive (PV+) interneurons, are believed to play key roles in the hippocampal oscillogenesis, we asked whether AβO selectively impairs these SST+ and PV+ interneurons. To selectively manipulate SST+ or PV+ interneuron activity in mice with AβO pathologyin vivo, we co-injected AβO and adeno-associated virus (AAV) for expressing floxed channelrhodopsin-2 (ChR2) into the hippocampus of SST-Cre or PV-Cre mice. Local field potential (LFP) recordingsin vivoin these AβO–injected mice showed a reduction in the peak power of theta oscillations and desynchronization of spikes from CA1 pyramidal neurons relative to theta oscillations compared to those in control mice. Optogenetic-activation of SST+ but not PV+ interneurons in AβO–injected mice fully restored the peak power of theta oscillations and resynchronized the theta spike phases to a level observed in control mice.In vitrowhole-cell voltage-clamp recordings in CA1 pyramidal neurons in hippocampal slices treated with AβO revealed that short-term plasticity of SST+ interneuron inhibitory inputs to CA1 pyramidal neurons at theta frequency were selectively disrupted while that of PV+ interneuron inputs were unaffected. Together, our results suggest that dysfunction in inputs from SST+ interneurons to CA1 pyramidal neurons may underlie the impairment of theta oscillations observed in AβO-injected micein vivo.Our findings identify SST+ interneurons as a target for restoring theta-frequency oscillations in early AD.


1996 ◽  
Vol 739 (1-2) ◽  
pp. 192-200 ◽  
Author(s):  
Franco Marrosu ◽  
Casimir A. Fornal ◽  
Christine W. Metzler ◽  
Barry L. Jacobs

2019 ◽  
Author(s):  
Umesh Vivekananda ◽  
Daniel Bush ◽  
James A Bisby ◽  
Sallie Baxendale ◽  
Roman Rodionov ◽  
...  

AbstractHippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations during spatial memory function, and how this relates to subsequent behaviour. Here we asked ten human epilepsy patients undergoing intracranial EEG recording to perform a desk-top virtual reality spatial memory task, and found that increased theta power in two discrete bands (‘low’ 2-5Hz and ‘high’ 6-9Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between ‘low’ theta phase and gamma amplitude during the same period was associated with improved task performance. These results support a role of theta oscillations and theta-gamma phase-amplitude coupling in human spatial memory function.


2011 ◽  
Vol 106 (5) ◽  
pp. 2749-2763 ◽  
Author(s):  
Hao Zhang ◽  
Shih-Chieh Lin ◽  
Miguel A. L. Nicolelis

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.


1969 ◽  
Vol 24 (2) ◽  
pp. 580-582 ◽  
Author(s):  
Thomas L. Bennett

Adey and his associates have asserted that theta electrical activity recorded from the hippocampus during learning and performance reflects the role of this structure in information processing, decision making and memory consolidation. This notion was recently questioned by Douglas (1967) who concluded that the tasks employed by Adey and his associates to assess theta activity were tasks which the lesion literature indicated do not requite hippocampal functioning to be learned. The present paper questions Douglas' assertion by describing studies in the lesion literature which demonstrate that the tasks used by Adey and his co-workers may actually require hippocampal functioning to be learned.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Víctor J López-Madrona ◽  
Elena Pérez-Montoyo ◽  
Efrén Álvarez-Salvado ◽  
David Moratal ◽  
Oscar Herreras ◽  
...  

Hippocampal firing is organized in theta sequences controlled by internal memory processes and by external sensory cues, but how these computations are coordinated is not fully understood. Although theta activity is commonly studied as a unique coherent oscillation, it is the result of complex interactions between different rhythm generators. Here, by separating hippocampal theta activity in three different current generators, we found epochs with variable theta frequency and phase coupling, suggesting flexible interactions between theta generators. We found that epochs of highly synchronized theta rhythmicity preferentially occurred during behavioral tasks requiring coordination between internal memory representations and incoming sensory information. In addition, we found that gamma oscillations were associated with specific theta generators and the strength of theta-gamma coupling predicted the synchronization between theta generators. We propose a mechanism for segregating or integrating hippocampal computations based on the flexible coordination of different theta frameworks to accommodate the cognitive needs.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Tim James Viney ◽  
Minas Salib ◽  
Abhilasha Joshi ◽  
Gunes Unal ◽  
Naomi Berry ◽  
...  

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.


2011 ◽  
Vol 105 (4) ◽  
pp. 1747-1755 ◽  
Author(s):  
Andrew J. Watrous ◽  
Itzhak Fried ◽  
Arne D. Ekstrom

Previous rodent studies demonstrate movement-related increases in theta oscillations, and recent evidence suggests that multiple navigationally relevant variables are reflected in this activity. Human invasive recordings have revealed movement-related modulations in delta and theta activity, although it is unclear whether additional behavioral variables are responsible for modulating this neural activity during navigation. We tested the role of delta and theta oscillations during navigation by addressing whether spatial-related processing, in addition to speed and task variables, modulates delta and theta activity. Recording from 317 hippocampal intracranial electrodes in 10 patients undergoing seizure monitoring, we observed increasing delta and theta power with increasing virtual speed at significantly more electrodes than would be expected by chance, replicating previous findings in nonhuman mammals. Delta and theta power were more consistently modulated, however, as a function of spatial view, including when subjects looked at stores in the virtual environment both to find a relevant goal or for spatial updating. A significantly larger proportion of electrodes showed view-related effects than speed-related modulations. Although speed, task, and spatial view affected delta and theta activity, individual electrodes were most frequently modulated by only one variable, rather than a combination of variables. These electrodes likely sampled independent delta and theta generators, which reflected movement-related and allocentric processing, respectively. These results extend previous findings in nonhuman mammals and humans, expanding our knowledge of the role of human hippocampal low-frequency oscillations in navigation.


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