scholarly journals Enhanced hippocampal type II theta activity AND altered theta architecture in mice lacking the Cav3.2 T-type voltage-gated calcium channel

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Muhammad Imran Arshaad ◽  
Magdalena Elisabeth Siwek ◽  
Christina Henseler ◽  
Johanna Daubner ◽  
Dan Ehninger ◽  
...  

AbstractT-type Ca2+ channels are assumed to contribute to hippocampal theta oscillations. We used implantable video-EEG radiotelemetry and qPCR to unravel the role of Cav3.2 Ca2+ channels in hippocampal theta genesis. Frequency analysis of spontaneous long-term recordings in controls and Cav3.2−/− mice revealed robust increase in relative power in the theta (4–8 Hz) and theta-alpha (4–12 Hz) ranges, which was most prominent during the inactive stages of the dark cycles. Urethane injection experiments also showed enhanced type II theta activity and altered theta architecture following Cav3.2 ablation. Next, gene candidates from hippocampal transcriptome analysis of control and Cav3.2−/− mice were evaluated using qPCR. Dynein light chain Tctex-Type 1 (Dynlt1b) was significantly reduced in Cav3.2−/− mice. Furthermore, a significant reduction of GABA A receptor δ subunits and GABA B1 receptor subunits was observed in the septohippocampal GABAergic system. Our results demonstrate that ablation of Cav3.2 significantly alters type II theta activity and theta architecture. Transcriptional changes in synaptic transporter proteins and GABA receptors might be functionally linked to the electrophysiological phenotype.

2019 ◽  
Vol 317 (5) ◽  
pp. C953-C963 ◽  
Author(s):  
Fengling Yuan ◽  
Jiejun Zhou ◽  
Lingxiu Xu ◽  
Wenxin Jia ◽  
Lei Chun ◽  
...  

GABA, a prominent inhibitory neurotransmitter, is best known to regulate neuronal functions in the nervous system. However, much less is known about the role of GABA signaling in other physiological processes. Interestingly, recent work showed that GABA signaling can regulate life span via a metabotropic GABAB receptor in Caenorhabditis elegans. However, the role of other types of GABA receptors in life span has not been clearly defined. It is also unclear whether GABA signaling regulates health span. Here, using C. elegans as a model, we systematically interrogated the role of various GABA receptors in both life span and health span. We find that mutations in four different GABA receptors extend health span by promoting resistance to stress and pathogen infection and that two such receptor mutants also show extended life span. Different GABA receptors engage distinct transcriptional factors to regulate life span and health span, and even the same receptor regulates life span and health span via different transcription factors. Our results uncover a novel, profound role of GABA signaling in aging in C. elegans, which is mediated by different GABA receptors coupled to distinct downstream effectors.


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

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.


2018 ◽  
Author(s):  
Hadijat M. Makinde ◽  
Talia B. Just ◽  
Deborah R. Winter ◽  
Steven J. Schwulst

Traumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injury, or concussions, may lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this subsequent neurologic impairment. Despite this, a microglia-specific injury signature has yet to be identified. In the current study we hypothesized that TBI-associated microglia would adopt longitudinal changes in their transcriptional profile associated with pathways linked to the development of motor, cognitive, and behavioral disorders. C57BL/6 mice underwent TBI via a controlled cortical impact and were followed longitudinally. FACSorted microglia from TBI mice were subjected to RNA-sequencing at 7, 30, and 90 days post-injury. We identified 4 major patterns of gene expression corresponding to the host defense response, synaptic potentiation, lipid remodeling, and membrane polarization. In particular, significant upregulation of genes involved in long-term synaptic potentiation including Ptpn5, Shank3, and Sqstm1 were observed offering new insight into a previously unknown role of microglia in the weakening of synaptic efficacy between neurons after brain injury.


1969 ◽  
Vol 24 (3) ◽  
pp. 965-966 ◽  
Author(s):  
Thomas L. Bennett

Douglas' reply to Bennett's criticism is discussed. The author concluded that Douglas may be correct in questioning Adey's hypothesis that hippocampal theta activity reflects the role of this structure in mediating the learning process but not on the basis of many of the arguments Douglas has made.


2021 ◽  
Vol 14 (670) ◽  
pp. eabb5235 ◽  
Author(s):  
Amy E. Pomeroy ◽  
Matthew I. Peña ◽  
John R. Houser ◽  
Gauri Dixit ◽  
Henrik G. Dohlman ◽  
...  

Cells use signaling pathways to receive and process information about their environment. These nonlinear systems rely on feedback and feedforward regulation to respond appropriately to changing environmental conditions. Mathematical models describing signaling pathways often lack predictive power because they are not trained on data that encompass the diverse time scales on which these regulatory mechanisms operate. We addressed this limitation by measuring transcriptional changes induced by the mating response in Saccharomyces cerevisiae exposed to different dynamic patterns of pheromone. We found that pheromone-induced transcription persisted after pheromone removal and showed long-term adaptation upon sustained pheromone exposure. We developed a model of the regulatory network that captured both characteristics of the mating response. We fit this model to experimental data with an evolutionary algorithm and used the parameterized model to predict scenarios for which it was not trained, including different temporal stimulus profiles and genetic perturbations to pathway components. Our model allowed us to establish the role of four architectural elements of the network in regulating gene expression. These network motifs are incoherent feedforward, positive feedback, negative feedback, and repressor binding. Experimental and computational perturbations to these network motifs established a specific role for each in coordinating the mating response to persistent and dynamic stimulation.


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.


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