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Selectively increasing GHS-R1a expression in dCA1 excitatory/inhibitory neurons have opposite effects on memory
Nan Li1, Na Li1, Fenghua Xu1
1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, Qingdao, 266071, Shandong, China.
Molecular Brain
|October 13, 2021
Summary
Selective increase of growth hormone secretagogue receptor 1a (GHS-R1a) in hippocampal excitatory neurons impaired memory, while increasing it in inhibitory neurons enhanced memory. This reveals a neuron-type-specific role for GHS-R1a in memory regulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Cognitive Science
Background:
- The growth hormone secretagogue receptor 1a (GHS-R1a) is present in the brain, including the hippocampus.
- Ghrelin/GHS-R1a signaling in the hippocampus is crucial for synaptic function, memory, and Alzheimer's disease (AD) related cognitive decline.
- Existing research on GHS-R1a's role in memory is inconsistent, and the precise mechanisms remain unclear.
Purpose of the Study:
- To investigate the direct impact of selectively increasing GHS-R1a expression in hippocampal CA1 (dCA1) excitatory and inhibitory neurons on learning and memory.
- To elucidate the neuron-type-specific functions of GHS-R1a signaling in memory modulation.
Main Methods:
- Assessed endogenous GHS-R1a distribution in dCA1 excitatory/inhibitory neurons using fluorescence in situ hybridization.
- Utilized stereotaxic injection of AAV vectors to achieve Cre-dependent GHS-R1a overexpression in specific neuronal populations of vGlut1-Cre (excitatory) or Dlx5/6-Cre (inhibitory) mice.
- Confirmed GHS-R1a upregulation via quantitative RT-PCR and evaluated long-term memory using various behavioral tests.
Main Results:
- GHS-R1a is expressed in both dCA1 excitatory pyramidal neurons and inhibitory interneurons.
- Selective GHS-R1a overexpression in dCA1 excitatory neurons led to impaired spatial and object-place recognition memory.
- Conversely, selective GHS-R1a overexpression in dCA1 inhibitory neurons resulted in enhanced long-term memory.
Conclusions:
- This study demonstrates, for the first time, a neuron-type-specific role for hippocampal GHS-R1a signaling in memory regulation.
- Targeting GHS-R1a expression or activity in distinct neuronal subpopulations could help resolve conflicting findings and clarify the mechanisms of memory control by ghrelin/GHS-R1a signaling.
- These insights are relevant for understanding memory under physiological conditions and in pathological states like Alzheimer's disease.
