Focal Dorsal Hippocampal Nav1.1 Knock Down Alters Place Cell Temporal Coordination and Spatial Behavior

Area of Science:

• Neuroscience
• Molecular Biology
• Neurodegenerative Diseases

Background:

• Voltage-gated sodium channel Nav1.1 (SCN3A) alterations are linked to epilepsy, Alzheimer's, and autism.
• Reduced Nav1.1 expression is associated with decreased fast-spiking activity in inhibitory neurons (INs).
• INs are crucial for the temporal organization of neuronal discharge.

Purpose of the Study:

• To investigate the in vivo impact of Nav1.1 dysfunction on neuronal coordination.
• To determine if reduced Nav1.1 expression negatively affects hippocampal network activity and spatial behavior.

Main Methods:

• Induced focal Nav1.1 knock-down (KD) in the adult rat hippocampus using shRNA interference.
• Assessed behavioral performance in a spatial novelty recognition task.
• Recorded neuronal firing rates, hippocampal oscillations (theta/gamma coupling), and place cell properties (theta phase precession).

Main Results:

• Focal Nav1.1 KD decreased spatial novelty recognition performance and IN firing rates.
• Nav1.1 KD reduced theta/gamma coupling and shifted pyramidal cell theta phase preference.
• Spatial accuracy and temporal coding of place cells, including theta phase precession, were degraded.

Conclusions:

• Nav1.1 deficit significantly alters temporal coordination of neuronal firing in the hippocampus (CA1).
• Impaired neuronal coordination due to Nav1.1 dysfunction negatively impacts behaviors dependent on hippocampal network integrity.
• Highlights the critical role of local inhibition in neuronal coordination and its relevance to pathological conditions.