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Deciphering midbrain mechanisms underlying prepulse inhibition of startle
Niveen Fulcher1, Erin Azzopardi2, Cleusa De Oliveira2
1University of Western Ontario, Schulich School of Medicine & Dentistry, Neuroscience Graduate Program, London, ON, N6A 5C1 Canada.
Progress in Neurobiology
|December 22, 2019
Summary
Prepulse inhibition (PPI) deficits are common in schizophrenia. This study found the pedunculopontine tegmental nucleus (PPTg) is involved in PPI, but not via its cholinergic neurons, suggesting other midbrain pathways are implicated.
Area of Science:
- Neuroscience
- Psychiatry
- Behavioral Science
Background:
- Prepulse inhibition (PPI) is a key sensorimotor gating measure.
- PPI deficits are characteristic of schizophrenia and autism spectrum disorder.
- The neural circuitry of PPI remains incompletely understood, challenging existing hypotheses.
Purpose of the Study:
- To investigate the role of the pedunculopontine tegmental nucleus (PPTg) in PPI.
- To determine if cholinergic neurons within the PPTg mediate PPI.
- To explore PPTg involvement using a chemogenetic approach.
Main Methods:
- Chemogenetic manipulation using inhibitory DREADDs in the PPTg.
- Systemic administration of clozapine-N-oxide (CNO) to activate DREADDs.
- Assessment of PPI and morphine-induced conditioned place preference (CPP).
Main Results:
- Inhibiting the entire PPTg disrupted PPI, confirming its involvement.
- Inhibiting specific cholinergic PPTg neurons did not affect PPI.
- Cholinergic neuron inhibition did affect morphine-induced CPP, validating DREADD efficacy.
Conclusions:
- The PPTg plays a role in sensorimotor gating (PPI).
- Cholinergic neurons in the PPTg are not essential for mediating PPI.
- Non-cholinergic neurons within or near the PPTg likely contribute to PPI mechanisms.

