Aging of the trigeminal blink system.

This study characterizes trigeminal blinks in normal human subjects between 20 and 80 years of age, 60-year-old Parkinson's disease patients, and young and old guinea pigs. In normal humans over 60 years of age, lid-closing duration, and the excitability and latency of the trigeminal reflex blink increase significantly relative to younger subjects. Aged guinea pigs appear to display similar increases in reflex blink duration and latency. Reflex blink amplitude, however, does not change consistently with age. For subjects less than 70 years of age, a unilateral trigeminal stimulus evokes a 37% larger blink in the eyelid ipsilateral to the stimulus than in the contralateral eyelid, but 70-year-olds exhibit blinks of equal amplitude. In all cases, blink duration is identical for the two eyelids. If normal, age-related loss of dopamine neurons explains these trigeminal blink modifications, then Parkinson's disease should exaggerate age-related changes in these blink parameters. Preliminary data show that Parkinson's disease increases blink duration and excitability relative to age-matched control subjects. Thus, it seems likely that normal, age-related loss of dopamine neurons accounts for increases in trigeminal blink excitability and duration. A previously uncharacterized type of trigeminally evoked blink appears after age 40 in humans and in aged guinea pigs. In subjects less than 40 years old, a single trigeminal stimulus elicits a single reflex blink. In subjects over age 40, however, a single stimulus frequently evokes a reflex blink and additional blinks that occur at a fixed interval relative to the preceding blink. These "blink oscillations" may arise from oscillatory processes within trigeminal reflex blink circuits. The presence of exaggerated blink oscillations in subjects with dry eye and benign essential blepharospasm suggests that an alteration of blink oscillation mechanisms plays a critical role in these disorders.

Reflex excitability regulates prepulse inhibition.

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.

EPSP amplitude modulation at the rat Ia-alpha motoneuron synapse: effects of GABAB receptor agonists and antagonists.

The object of this study was to examine the relationship between excitatory postsynaptic potential (EPSP) amplitude, posttetanic potentiation, and EPSP amplitude modulation at synapses made by group Ia afferents on motoneurons in the rat. These relationships were evaluated in cells in untreated rats and in cells in rats treated with the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen and antagonist CGP-35348, which were used to manipulate Ca2+ entry into presynaptic terminals and consequently probability of transmitter release from them. There was no evidence for postsynaptic action of these drugs from measurement of their effects on motoneuron properties. During high-frequency stimulation (32 shock bursts at 167 Hz), EPSP amplitude either decreased (negative modulation) or increased (positive modulation) in response to successive stimuli at different connections. In untreated rats this frequency-dependent amplitude modulation behavior was inversely but weakly correlated with EPSP amplitude measured at low frequency. Intravenous (iv) administration of the GABAB agonist, baclofen, produced a marked and progressive decrease in EPSP amplitude measured at low frequency coincident with a change in frequency-dependent EPSP amplitude modulation toward more positive values (synaptic facilitation). In contrast, an increase in EPSP amplitude occurred after iv administration of the GABAB antagonist CGP-35348 that was accompanied by a negative shift in EPSP amplitude modulation during high-frequency stimulation. The negative shift in EPSP amplitude modulation (synaptic depression) after CGP-35348 application was much smaller than the positive shift induced by baclofen when normalized to the change in EPSP amplitude. Posttetanic potentiation decreased after baclofen but did not increase after CGP-35348. The relationship between modulation and EPSP amplitude was much steeper after GABAB receptor manipulation in either direction than that observed in the population of motoneurons in untreated preparations. This suggests that in the rat differences in probability of release play at most a small role in determining EPSP amplitude across the motoneuron pool.

Differences in the connectivity of rat pudendal motor nuclei as revealed by retrograde transneuronal transport of wheat germ agglutinin.

Bilateral coordinated activation of pudendal motoneurons is an essential component of penile reflexes in male rats. However, little is known about the intraspinal organization of these reflexes. In the present study, retrograde transneuronal transport of wheat germ agglutinin (WGA) was used to examine the organization of spinal motoneurons and putative interneurons mediating penile reflexes in adult male rats. Injection of WGA into the ventral bulbospongiosus muscle resulted in direct retrograde labeling of motoneurons in the ipsilateral dorsomedial (DM) nucleus and transneuronal labeling of ipsilateral and contralateral DM motoneurons. Motoneurons in the ipsilateral and contralateral dorsolateral (DL) nuclei were not labeled. WGA-labeled putative interneurons were observed bilaterally, primarily in the ventromedial spinal gray matter extending dorsally to the central canal and the dorsal gray commissure. The number of transneuronally labeled putative interneurons increased with longer survival times. Injection of WGA into the ischiocavernosus muscle resulted in direct retrograde labeling of motoneurons in the medial subdivision of the ipsilateral DL nucleus. However, no WGA labeling was detected in motoneurons in the lateral subdivision of the ipsilateral DL nucleus, the contralateral DL nucleus, or the DM nuclei at any of the survival times studied (1-7 days). Only a small number of transneuronally labeled putative interneurons was observed in the ventrolateral gray matter at longer survival times (3-7 days). Thus, marked differences were observed between the DM and DL nuclei with respect to the transneuronal transport of WGA. These results are discussed with respect to the organization of the spinal circuits that mediate pudendal motor reflexes.