Age-related Changes in Lateral Entorhinal and CA3 Neuron Allocation Predict Poor Performance on Object Discrimination

Area of Science:

• Neuroscience
• Aging Research
• Cognitive Science

Background:

• Age-related memory deficits are linked to CA3 hippocampal dysfunction, including hyperactivity.
• The role of afferent input, specifically from the lateral entorhinal cortex (LEC), to CA3 in aging remains unclear.
• Understanding how advanced age affects LEC activity and its response to environmental changes is crucial for cognitive decline research.

Purpose of the Study:

• To investigate the impact of advanced age on LEC neuronal activity and its contribution to CA3 hyperactivity.
• To determine if age-related deficits in sensory discrimination are related to CA3 neuronal inability to update activity in new environments.
• To explore the relationship between LEC activity, CA3 function, and cognitive performance in aged animals.

Main Methods:

• Young and aged rats were tested on a LEGO object discrimination task.
• Cellular activity in the CA3 region was analyzed using fluorescence in situ hybridization for the immediate-early gene Arc.
• Retrograde tracer choleratoxin B (CTB) was used to identify afferent neurons from LEC to CA3.

Main Results:

• Poor performers in the object discrimination task among aged rats showed higher CA3 neuronal activity in a novel environment.
• This hyperactivity in aged poor performers was not linked to the ability of CA3 neurons to remap.
• Aged rats with poor object discrimination also exhibited increased Arc mRNA in LEC neurons projecting to CA3.

Conclusions:

• The lateral entorhinal cortex (LEC) contributes to CA3 hyperactivity in aged rats with object discrimination deficits.
• Age-related cognitive decline may stem from network-wide dysfunction, including afferent pathways like the LEC.
• These findings highlight the importance of studying the entire neural network, not just isolated regions, in understanding cognitive aging.