Reflex Excitability Regulates Prepulse Inhibition

Abstract

Presentation of a weak stimulus, a prepulse, before a reflex-evoking stimulus decreases the amplitude of the reflex response relative to reflex amplitude evoked without a preceding prepulse. For example, presenting a brief tone before a trigeminal blink-eliciting stimulus significantly reduces reflex blink amplitude. A common explanation of such data are that sensory processing of the prepulse modifies reflex circuit behavior. The current study investigates the converse hypothesis that the intrinsic characteristics of the reflex circuit rather than prepulse processing determine prepulse modification of trigeminal and acoustic reflex blinks. Unilateral lesions of substantia nigra pars compacta neurons created rats with hyperexcitable trigeminal reflex blinks but normally excitable acoustic reflex blinks. In control rats, presentation of a prepulse reduced the amplitude of both trigeminal and acoustic reflex blinks. In 6-OHDA-lesioned rats, however, the same acoustic prepulse facilitated trigeminal reflex blinks but inhibited acoustic reflex blinks. The magnitude of prepulse modification correlated with reflex excitability. Humans exhibited the same pattern of prepulse modification. An acoustic prepulse facilitated the trigeminal reflex blinks of subjects with hyperexcitable trigeminal reflex blinks caused by Parkinson's disease. The same prepulse inhibited trigeminal reflex blinks of age-matched control subjects. Prepulse modification also correlated with trigeminal reflex blink excitability. These data show that reflex modification by a prepulse reflects the intrinsic characteristics of the reflex circuit rather than an external adjustment of the reflex circuit by the prepulse.

Blink-related sensorimotor anatomy in the rat

“…In recent years, the rat has become an important model system for studying dry eye (Fujihara et al 2001), sensory processing in the trigeminal nucleus (Meng et al 1997(Meng et al , 2000, basic mechanisms of motor learning (Weiss et al 1991;Pellegrini and Evinger 1997;Powers et al 1997;Nicholson and Freeman 2000;Schicatano et al 2000) and blepharospasm . Interpretation and further development of these models is dependent on a complete description of rat eyelid and corneal innervation, particularly as it pertains to blinking.…”

Human Central Nervous System Circuits Examined in Patients with Parkinson's Disease Using the Electrodes Implanted for Deep Brain Stimulation

“…One of the subcortical circuits of interest in PD is the one responsible for prepulse inhibition (Fendt et al, 2001). The abnormally reduced prepulse inhibition in PD patients (Schicatano et al, 2000;VallsSolé et al, 2004) reflects in part disturbed sensorimotor integration, but the normality of the effects when DBS is used as prepulse indicate that the defect does not lie ahead of the structures activated by the stimulus. We cannot assume that the circuit of prepulse inhibition is the same with DBS and with auditory or somatosensory stimuli.…”

“…The abnormally enhanced excitability recovery after a conditioning stimulus (Kimura, 1973) was found to decrease progressively at intervals of 1, 3, and 6 months after surgery, suggesting that GPi DBS results in functional reorganization of the nervous system and a long-term increase in brainstem inhibition. Another dysfunction seen in the recording of the blink reflexes in PD patients is reduced prepulse inhibition (Schicatano et al, 2000;Valls-Solé et al, 2004). The pathophysiology of this phenomenon is not clarified but the abnormalities observed in PD may be due to a dysfunction in the connections between the basal ganglia and the brainstem nuclei, particularly the PPN (Pahapill and Lozano, 2000).…”

Sensorimotor integration in patients with parkinsonian type multisystem atrophy

“…The nucleus reticularis pontis caudalis (nRPC) which is connected with the PPTn may play a key role in presynaptic inhibition of trigeminal afferent terminals [20,45,52,63]. The SC, which projects to the nucleus raphe magnus (NRM) and receives inputs from different sensory modalities may have a role in a tonic and phasic control of blink reflex circuit excitability [2,3,14,49]. The SC and the PPTn functional activity can be in turn regulated by basal ganglia outputs via substantia nigra pars reticulata [2,3,20].…”