scholarly journals Functional Coupling of BK Channels to NMDA Receptors in Hippocampal Dentate Gyrus

2017 ◽  
Vol 112 (3) ◽  
pp. 112a ◽  
Author(s):  
Xin Guan ◽  
Jiyuan Zhang ◽  
Qin Li ◽  
Hui-Lin Pan ◽  
Jiusheng Yan
Keyword(s):  
Dentate Gyrus ◽  
Nmda Receptors ◽  
Bk Channels ◽  
Functional Coupling ◽  
Hippocampal Dentate Gyrus

scholarly journals Glutamate-activated BK channel complexes formed with NMDA receptors

2018 ◽  
Vol 115 (38) ◽  
pp. E9006-E9014 ◽  
Author(s):  
Jiyuan Zhang ◽  
Xin Guan ◽  
Qin Li ◽  
Andrea L. Meredith ◽  
Hui-Lin Pan ◽  
...  
Keyword(s):  
Complex Formation ◽  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
Nmda Receptors ◽  
Bk Channels ◽  
Bk Channel ◽  
Functional Coupling ◽  
Physical Interaction ◽  
Patch Clamp Recording ◽  
Channel Activation

The large-conductance calcium- and voltage-activated K+ (BK) channel has a requirement of high intracellular free Ca2+ concentrations for its activation in neurons under physiological conditions. The Ca2+ sources for BK channel activation are not well understood. In this study, we showed by coimmunopurification and colocalization analyses that BK channels form complexes with NMDA receptors (NMDARs) in both rodent brains and a heterologous expression system. The BK–NMDAR complexes are broadly present in different brain regions. The complex formation occurs between the obligatory BKα and GluN1 subunits likely via a direct physical interaction of the former’s intracellular S0–S1 loop with the latter’s cytosolic regions. By patch-clamp recording on mouse brain slices, we observed BK channel activation by NMDAR-mediated Ca2+ influx in dentate gyrus granule cells. BK channels modulate excitatory synaptic transmission via functional coupling with NMDARs at postsynaptic sites of medial perforant path-dentate gyrus granule cell synapses. A synthesized peptide of the BKα S0–S1 loop region, when loaded intracellularly via recording pipette, abolished the NMDAR-mediated BK channel activation and effect on synaptic transmission. These findings reveal the broad expression of the BK–NMDAR complexes in brain, the potential mechanism underlying the complex formation, and the NMDAR-mediated activation and function of postsynaptic BK channels in neurons.

scholarly journals Structural and Functional Coupling between BK Channels and NMDA Receptors

2016 ◽  
Vol 110 (3) ◽  
pp. 289a
Author(s):  
Jiyuan Zhang ◽  
Qin Li ◽  
Xin Guan ◽  
Hui-Lin Pan ◽  
Jiusheng Yan
Keyword(s):  
Nmda Receptors ◽  
Bk Channels ◽  
Functional Coupling

scholarly journals Knockout of the BK β4-subunit promotes a functional coupling of BK channels and ryanodine receptors that mediate a fAHP-induced increase in excitability

2016 ◽  
Vol 116 (2) ◽  
pp. 456-465 ◽  
Author(s):  
Bin Wang ◽  
Vladislav Bugay ◽  
Ling Ling ◽  
Hui-Hsui Chuang ◽  
David B. Jaffe ◽  
...  
Keyword(s):  
Action Potential ◽  
Dentate Gyrus ◽  
Ryanodine Receptor ◽  
Bk Channels ◽  
Bk Channel ◽  
Functional Coupling ◽  
Current Clamp ◽  
Channel Activation ◽  
Repolarization Phase

BK channels are large-conductance calcium- and voltage-activated potassium channels with diverse properties. Knockout of the accessory BK β4-subunit in hippocampus dentate gyrus granule neurons causes BK channels to change properties from slow-gated type II channels to fast-gated type I channels that sharpen the action potential, increase the fast afterhyperpolarization (fAHP) amplitude, and increase spike frequency. Here we studied the calcium channels that contribute to fast-gated BK channel activation and increased excitability of β4 knockout neurons. By using pharmacological blockers during current-clamp recording, we find that BK channel activation during the fAHP is dependent on ryanodine receptor activation. In contrast, L-type calcium channel blocker (nifedipine) affects the BK channel-dependent repolarization phase of the action potential but has no effect on the fAHP. Reducing BK channel activation during the repolarization phase with nifedipine, or during the fAHP with ryanodine, indicated that it is the BK-mediated increase of the fAHP that confers proexcitatory effects. The proexcitatory role of the fAHP was corroborated using dynamic current clamp. Increase or decrease of the fAHP amplitude during spiking revealed an inverse relationship between fAHP amplitude and interspike interval. Finally, we show that the seizure-prone ryanodine receptor gain-of-function (R2474S) knockin mice have an unaltered repolarization phase but larger fAHP and increased AP frequency compared with their control littermates. In summary, these results indicate that an important role of the β4-subunit is to reduce ryanodine receptor-BK channel functional coupling during the fAHP component of the action potential, thereby decreasing excitability of dentate gyrus neurons.

scholarly journals Hippocampal dentate gyrus coordinates brain-wide communication and memory updating through an inhibitory gating

2020 ◽  
Author(s):  
José María Caramés ◽  
Elena Pérez-Montoyo ◽  
Raquel Garcia-Hernandez ◽  
Santiago Canals
Keyword(s):  
Dentate Gyrus ◽  
Brain Regions ◽  
Functional Coupling ◽  
Subcortical Structures ◽  
Hippocampal Dentate Gyrus ◽  
Memory Processing ◽  
Neuronal Populations ◽  
Brain Fmri ◽  
Interneuron Activity

AbstractDistinct forms of memory processing are often causally identified with specific brain regions, but a key facet of memory processing includes linking separated neuronal populations. Using cell-specific manipulations of inhibitory neuronal activity, we discovered a key role of the dentate gyrus (DG) in coordinating dispersed neuronal populations during memory formation. In whole-brain fMRI and electrophysiological experiments, we found that parvalbumin (PV) interneurons in the DG control the functional coupling of the hippocampus within a wider network of neocortical and subcortical structures including the prefrontal cortex (PFC) and the nucleus accumbens (NAc). In a novel object-location task, regulation of PV interneuron activity enhanced or prevented memory encoding and, without effect upon the total number of task activated c-Fos+ cells, revealed a correlation between activated neuronal populations in the hippocampus-PFC-NAc network. These data suggest a critical regulatory role of PV interneurons in the dentate gyrus in brain-wide polysynaptic communication channels and the association of cell assemblies across multiple brain regions.

Malfunctional Reorganization in the Developing Limbo-Prefrontal System in Animals: Implications for Human Psychoses?

2001 ◽  
Vol 12 (1) ◽  
pp. 8-14
Author(s):  
Gertraud Teuchert-Noodt ◽  
Ralf R. Dawirs
Keyword(s):  
Prefrontal Cortex ◽  
Mental Disorders ◽  
Dentate Gyrus ◽  
Cognitive Functions ◽  
Experimental Approach ◽  
Regulatory Mechanisms ◽  
Hippocampal Dentate Gyrus ◽  
Non Invasive ◽  
Invasive Method ◽  
Activity Dependent

Abstract: Neuroplasticity research in connection with mental disorders has recently bridged the gap between basic neurobiology and applied neuropsychology. A non-invasive method in the gerbil (Meriones unguiculus) - the restricted versus enriched breading and the systemically applied single methamphetamine dose - offers an experimental approach to investigate psychoses. Acts of intervening affirm an activity dependent malfunctional reorganization in the prefrontal cortex and in the hippocampal dentate gyrus and reveal the dopamine position as being critical for the disruption of interactions between the areas concerned. From the extent of plasticity effects the probability and risk of psycho-cognitive development may be derived. Advance may be expected from insights into regulatory mechanisms of neurogenesis in the hippocampal dentate gyrus which is obviously to meet the necessary requirements to promote psycho-cognitive functions/malfunctions via the limbo-prefrontal circuit.

Sign in / Sign up

Export Citation Format

Share Document