자료유형  

 학위논문

Control Number  

0017160501

International Standard Book Number  

9798381959642

Dewey Decimal Classification Number  

574.191

Main Entry-Personal Name  

Shu, Wen-Chi.

Publication, Distribution, etc. (Imprint  

[S.l.] : The University of Wisconsin - Madison., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

82 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-09, Section: B.

General Note  

Advisor: Jackson, Meyer B.

Dissertation Note  

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2024.

Summary, Etc.  

요약The repetitive firing of granule cells (GCs) in the dentate gyrus (DG) facilitates synaptic transmission to the CA3 region, allowing for the gating and amplification of information flow through the hippocampus. High-frequency bursts in the DG are associated with behavior and plasticity, even though GCs do not readily burst. Under normal conditions, a single shock to the perforant path typically induces a single spike in a GC, with multiple spikes occurring only occasionally. The mechanism underlying this simplest form of bursting and its role in animal behavior remain poorly understood. In this study, we expand our understanding of GC multiple spiking by employing a hybrid genetically-encoded voltage sensor, hVoS 1.5, to simultaneously monitor voltage changes in mature GCs and behaviorally-activated GCs in hippocampal slices. This approach allowed us to visualize synaptically-evoked responses of many GCs simultaneously, which is particularly beneficial for detecting relatively infrequent double and triple spikes.We first investigated the mechanism of multiple spiking in mature GCs targeted by transient Prox1-Cre activation early in development. Our findings indicate that GCs in both coronal and transverse slices independently generate double spikes in approximately 5% of trials. Blockade of GABAA receptors increased the incidence of multiple spikes and extended the inter-spike interval, suggesting that inhibitory interneurons limit repetitive spiking and set the time window for successive spikes. Inhibiting synaptic glutamate release revealed that recurrent excitation mediated by hilar mossy cells contributes to, but is not necessary for, multiple spiking. Blockade of T-type Ca2+ channels did not reduce multiple spiking but prolonged inter-spike intervals. Voltage imaging in different GC compartments showed that second spikes can be initiated in either dendrites or somata. Thus, our pharmacological and biophysical experiments highlight the roles of both synaptic circuitry and intrinsic excitability in GC repetitive spiking.As GC bursts have been proposed to encode information during distinct behaviors, we employed a genetic strategy to drive probe expression with Cre recombinase under temporal control of the c-fos gene in behaviorally-activated GCs. We used this approach to investigate the impact of experience on spiking behaviors. We observed broader spikes in active GCs from animals maintained in a home environment. Behaviorally-activated GCs exhibited heterogeneity, with some cells generating doublets more frequently. Novelty-activated GCs displayed doublets in approximately 5.8% of trials, which is about 1% higher than in home-activated GCs, suggesting that multiple-spiking behavior may play a role in encoding experience. When blocking GABAergic transmission, novelty-GC ensembles exhibited a 5-fold increase in doublet incidence and a significantly longer mean interval of 2.8 msec, while home-GC ensembles exhibited a 3-fold increase without a change in mean interval. Animal experience led to a shift in the interval distribution and in the dominant interval, indicating that the timing of subsequent spikes may be crucial for memory acquisition. This prolonged interval strongly depends on recurrent excitation. In conclusion, our data suggest that the generation of multiple spikes is regulated by the interplay of GC intrinsic excitability, recurrent inhibition, and recurrent excitation. Prior experience can alter GC multiple spiking, potentially playing a role in how behavior modifies DG processing.

Subject Added Entry-Topical Term  

Biophysics.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Neurosciences.

Index Term-Uncontrolled  

Burst

Index Term-Uncontrolled  

Dentate gyrus

Index Term-Uncontrolled  

Granule cells

Index Term-Uncontrolled  

Synaptic transmission

Added Entry-Corporate Name  

The University of Wisconsin - Madison Neuroscience

Host Item Entry  

Dissertations Abstracts International. 85-09B.

Electronic Location and Access  

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Control Number  

joongbu:658074