Gpr158 Deficiency Impacts Hippocampal CA1 Neuronal Excitability, Dendritic Architecture, and Affects Spatial Learning

Area of Science:

• Neuroscience
• Molecular Biology
• Synaptic Plasticity

Background:

• G-protein-coupled receptor 158 (Gpr158) is expressed in brain regions crucial for memory, including the hippocampus.
• Gpr158 plays a role in stress responses and has recently been identified as a synaptic organizer in the hippocampus.
• While Gpr158 is abundant in CA3, it is also present in CA1, particularly in adult mice.

Purpose of the Study:

• To investigate the impact of Gpr158 deficiency on the physiology and function of hippocampal CA1 neurons.
• To assess the behavioral consequences of Gpr158 loss on learning and memory.

Main Methods:

• Utilized hippocampal-dependent behavioral tests (Morris water maze, passive avoidance) in Gpr158 knockout (KO) mice.
• Performed electrophysiological recordings to analyze synaptic transmission and intrinsic excitability in CA1 pyramidal neurons.
• Conducted morphological analyses to examine dendritic architecture of CA1 neurons ex vivo and in vitro.

Main Results:

• Gpr158 KO mice exhibited deficits in spatial memory acquisition and retrieval, and extinction memory.
• Basal synaptic transmission in CA1 was normal, but Schaffer collateral-mediated postsynaptic currents were reduced.
• CA1 pyramidal neurons showed increased intrinsic excitability and significantly reduced apical dendritic complexity.
• A positive correlation was observed between spatial memory and dendritic complexity.

Conclusions:

• Gpr158 deficiency leads to significant disruptions in hippocampal CA1 neuronal dendritic architecture and physiology.
• Impaired dendritic morphology in Gpr158 KO mice correlates with deficits in spatial memory acquisition.
• Gpr158 is crucial for maintaining hippocampal CA1 neuronal structure and function, impacting cognitive abilities.