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Neonatal NMDA blockade alters the LTP, LTD and cognitive functions in male and female Wistar rats
Nastaran Golitabari1, Forouzan Mohammadian1, Ali-Akbar Salari2
1Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
Insights
Early life exposure to phencyclidine (PCP) impairs adult rat hippocampal synaptic plasticity and memory. Neonatal NMDA receptor blockade by PCP alters synaptic function, affecting long-term potentiation and depression in CA1 neurons.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Developmental Neurobiology
Background:
- Neonatal NMDA receptor blockade by phencyclidine (PCP) is linked to adult cognitive deficits.
- Limited understanding exists regarding early-life PCP effects on later synaptic function.
Purpose of the Study:
- To investigate the impact of early-life PCP exposure on the electrophysiologic function of hippocampal CA1 neurons in adult rats.
- To determine if neonatal PCP alters synaptic transmission, plasticity, and neuronal response profiles.
Main Methods:
- Wistar rats received neonatal PCP or saline on postnatal days 7, 9, and 11.
- Adult rats underwent behavioral and electrophysiological assessments of hippocampal CA1 neurons.
- Electrophysiology included basic synaptic transmission, frequency-following capacity, paired-pulse facilitation, LTP, and LTD.
Main Results:
- Neonatal PCP did not affect basic synaptic transmission but modestly impacted frequency-following capacity.
- PCP treatment significantly reduced paired-pulse facilitation in the Schaffer collateral-CA1 pathway.
- Long-term potentiation and depression were attenuated, with altered complex response profiles in adult rats.
- Results were consistent between sexes and correlated with impaired spatial memory.
Conclusions:
- Early-life NMDA receptor blockade by PCP significantly impairs adult hippocampal synaptic plasticity (LTP/LTD).
- Neonatal PCP exposure alters short-term synaptic dynamics and neuronal response complexity in adulthood.
- These synaptic alterations are associated with cognitive deficits, highlighting critical developmental periods for NMDA receptor function.
Abstract:
There is compelling evidence that neonatal blockade of NMDA receptors by phencyclidine (PCP) is associated with cognitive impairment in adulthood but little is known about the effects of early life PCP treatment on synaptic function later in life. Here, we sought to determine whether early life exposure to PCP alters the electrophysiologic function of hippocampal CA1 neurons in adult rats. To this end, male and female Wistar rats received either saline or PCP (10 mg/kg) on postnatal days (PND) 7, 9, and 11, and then underwent separate behavioral and electrophysiology tests in adulthood. Neonatal PCP treatment did not alter basic synaptic transmission and had only a modest effect on frequency following (FF) capacity but significantly decreased the paired-pulse facilitation (PPF) in the Schaffer collateral (SC)-CA1 pathway. We found that PCP treatment significantly attenuated the long-term potentiation (LTP) and long-term depression (LTD) in CA1 neurons accompanied by pronounced alteration in complex response profile in adult rats. The electrophysiology data were comparable in male and female rats and reliably associated with impaired spatial reference and working memories in these animals. Overall, this study suggests that blockade of NMDA receptors during early life deteriorates the short-term and long-term synaptic plasticity and complex response profile of CA1 neurons in adulthood.
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