BackgroundHigh-Runner (HR) mice, selectively bred for increased voluntary wheel running behavior, exhibit heightened motivation to run. Exercise has been shown to influence hippocampal long-term potentiation (LTP) and memory, and is neuroprotective in several neurodegenerative diseases. ObjectiveThis study aimed to determine the impact of intense running in HR mice with wheel access on hippocampal LTP, compared to HR mice without wheels and non-selected control (C) mice with/without wheels. Additionally, we investigated the involvement of D1/D5 receptors and the dopamine transporter (DAT) in LTP modulation and examined levels of these proteins in HR and C mice. MethodsAdult female HR and C mice were individually housed with/without running wheels for at least two weeks. Hippocampal LTP of extracellular field excitatory postsynaptic potentials (fEPSPs) was measured in area CA1, and SKF-38393 (D1/D5 receptor agonist) and GBR 12909 (DAT inhibitor) were used to probe the role of D1/D5 receptors and DAT in LTP differences. Western blot analyses assessed D1/D5 receptor and DAT expression in the hippocampus, prefrontal cortex, and cerebellum. ResultsHR mice with wheel access showed significantly increased hippocampal LTP compared to those without wheels and to C mice with/without wheels. Treatment with SKF-38393 or GBR 12909 prevented the heightened LTP in HR mice with wheels, aligning it with levels in C mice. Hippocampal D1/D5 receptor levels were lower, and DAT levels were higher in HR mice compared to C mice. No significant changes were observed in other brain regions. ConclusionsThe increased hippocampal LTP seen in HR mice with wheel access may be related to alterations in dopaminergic synaptic transmission that underlie the neurophysiological basis of hyperactivity, motor disorders, and/or motivation. 
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                            Developmental onset of enduring long‐term potentiation in mouse hippocampus
                        
                    
    
            Abstract Analysis of long‐term potentiation (LTP) provides a powerful window into cellular mechanisms of learning and memory. Prior work shows late LTP (L‐LTP), lasting >3 hr, occurs abruptly at postnatal day 12 (P12) in thestratum radiatumof rat hippocampal area CA1. The goal here was to determine the developmental profile of synaptic plasticity leading to L‐LTP in the mouse hippocampus. Two mouse strains and two mutations known to affect synaptic plasticity were chosen: C57BL/6J andFmr1−/yon the C57BL/6J background, and 129SVE andHevin−/−(Sparcl1−/−) on the 129SVE background. Like rats, hippocampal slices from all of the mice showed test pulse‐induced depression early during development that was gradually resolved with maturation by 5 weeks. All the mouse strains showed a gradual progression between P10‐P35 in the expression of short‐term potentiation (STP), lasting ≤1 hr. In the 129SVE mice, L‐LTP onset (>25% of slices) occurred by 3 weeks, reliable L‐LTP (>50% slices) was achieved by 4 weeks, andHevin−/−advanced this profile by 1 week. In the C57BL/6J mice, L‐LTP onset occurred significantly later, over 3–4 weeks, and reliability was not achieved until 5 weeks. Although some of theFmr1−/ymice showed L‐LTP before 3 weeks, reliable L‐LTP also was not achieved until 5 weeks. L‐LTP onset was not advanced in any of the mouse genotypes by multiple bouts of theta‐burst stimulation at 90 or 180 min intervals. These findings show important species differences in the onset of STP and L‐LTP, which occur at the same age in rats but are sequentially acquired in mice. 
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                            - Award ID(s):
- 1707356
- PAR ID:
- 10455245
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Hippocampus
- Volume:
- 30
- Issue:
- 12
- ISSN:
- 1050-9631
- Page Range / eLocation ID:
- p. 1298-1312
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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