Chronic Pb²⁺ Exposure Causes Hippocampal Network Hypersynchrony, Absence Seizures, and Sensorimotor Deficits

Area of Science:

• Neuroscience
• Environmental Health
• Neurotoxicology

Background:

• Chronic early-life lead (Pb²⁺) exposure is linked to cognitive deficits, behavioral issues, and adult psychopathology.
• Pb²⁺ acts as an N-methyl-D-aspartate receptor (NMDAR) antagonist, impacting neurodevelopment, including hippocampal (HC) interneurons and synaptic function.
• The effects of Pb²⁺ on HC network dynamics, crucial for linking cellular changes to cognitive outcomes, remain poorly understood.

Purpose of the Study:

• To investigate the impact of chronic early-life Pb²⁺ exposure on HC network dynamics in freely behaving rats.
• To assess the functional consequences of Pb²⁺-induced network alterations on prepulse inhibition of the acoustic startle reflex (PPI).

Main Methods:

• Recorded HC local field potentials (LFPs) in rats chronically exposed to Pb²⁺ during early life.
• Analyzed theta and gamma frequency band synchronization and their modulation by behavior.
• Assessed PPI in adult male and female rats exposed to Pb²⁺, examining sex-specific effects.

Main Results:

• Pb²⁺ exposure induced theta rhythmic hypersynchrony and amplified fast gamma synchronization in the HC.
• Behavioral modulation of theta and gamma rhythms was disrupted, and absence seizures (theta-frequency SWDs) were exacerbated.
• Adult males, but not females or juvenile males, exhibited reduced PPI, mirroring sex differences seen in schizophrenia.

Conclusions:

• Chronic early-life Pb²⁺ exposure dysregulates HC network rhythmic coordination.
• These network alterations are associated with impaired sensory gating (PPI) and may underlie cognitive deficits.
• The findings highlight Pb²⁺-induced neurodevelopmental toxicity and its relevance to psychiatric disorders.