Developmental Olfactory Dysfunction and Abnormal Odor Memory in Immune-Challenged Disc1^+/- Mice

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Neuronal activity in the olfactory bulb (OB) is crucial for developing the hippocampal-prefrontal network.
• Disruptions in OB output during early development can lead to cognitive deficits resembling neuropsychiatric disorders.

Purpose of the Study:

• To investigate OB activity during early development in a mouse model (immune-challenged Disc1+/- mice) mimicking genetic and environmental risk factors for neuropsychiatric disorders.
• To determine if OB activity disruptions contribute to hippocampal-prefrontal network dysfunction and memory impairments.

Main Methods:

• In vivo electrophysiology to record OB neuronal and network activity.
• Behavioral assessments to evaluate odor perception and long-term odor memory.
• Utilized immune-challenged Disc1+/- mice of both sexes to model dual etiology of neuropsychiatric disorders.

Main Results:

• Immune-challenged Disc1+/- mice exhibited reduced spontaneous neuronal and network activity in the OB during early development.
• This early OB deficit did not impact odor-evoked activity or perception.
• However, long-term odor memory was significantly impaired in these mice.

Conclusions:

• Reduced spontaneous activity in the developing OB may impair the maturation of the hippocampal-prefrontal network.
• This developmental deficit in OB-hippocampal-prefrontal connectivity may underlie memory impairments observed in immune-challenged Disc1+/- mice.
• Findings suggest a potential mechanism linking early-life olfactory system dysfunction to cognitive deficits in neuropsychiatric disorders.