Prepulse modulation of the startle reaction and the blink reflex in normal human subjects.

Blink reflexes are usually considered the most representative and consistent response of the auditory startle reaction (ASR), and they are often the only response evaluated in human psychophysiological studies. However, auditory stimuli also induce an auditory blink reflex (ABR), the physiological characteristics and brainstem circuitry of which may be different from those of the ASR. This study aimed to investigate whether there were differences between the orbicularis oculi (OOc) responses elicited with the ABR (OOcABR) and those elicited with the ASR (OOcASR) regarding their behavior to prepulse modulation. For comparison, we also examined the OOc responses to supraorbital nerve stimulation (OOcEBR). Electromyographic responses were simultaneously recorded from the OOc, masseter (MAS) and sternocleidomastoid (SCM) muscles. ABRs were considered when auditory stimuli induced responses limited to the OOc, and ASRs were considered when responses were induced in all muscles recorded from. Prepulse stimuli were either a weak electrical stimulation at the third finger (somatosensory prepulse) or a weak acoustic tone (auditory prepulse) that preceded the response-eliciting stimuli by intervals ranging from 0 to 200 ms. Prepulse effects differed according to prepulse modality, but the OOcABR and the OOcASR were always modulated in the same way. In both responses, somatosensory prepulses induced facilitation from 20 to 50 ms, followed by inhibition beyond 75 ms, and auditory prepulses induced no facilitation but a significant inhibition beyond 30 ms. In the OOcEBR, both somatosensory and acoustic prepulses induced facilitation of R1 and inhibition of R2 beyond 30 ms. Our results suggest that the OOcABR and the OOcASR exhibit the same physiological behavior regarding prepulse modulation. It is hypothesized that prepulse facilitation is due to direct impingement of subthreshold excitatory inputs onto the facial motoneurons while prepulse inhibition results from the engagement of a presynaptic inhibitory circuit in the brainstem.

Patterned ballistic movements triggered by a startle in healthy humans.

1. The reaction time to a visual stimulus shortens significantly when an unexpected acoustic startle is delivered together with the 'go' signal in healthy human subjects. In this paper we have investigated the physiological mechanisms underlying this effect. If the commands for the startle and the voluntary reaction were superimposed at some level in the CNS, then we would expect to see alterations in the configuration of the voluntary response. Conversely, if the circuit activated by the startling stimulus is somehow involved in the execution of voluntary movements, then reaction time would be sped up but the configuration of the motor programme would be preserved. 2. Fourteen healthy male and female volunteers were instructed to react as fast as possible to a visual 'go' signal by flexing or extending their wrist, or rising onto tiptoe from a standing position. These movements generated consistent and characteristic patterns of EMG activation. In random trials, the 'go' signal was accompanied by a very loud acoustic stimulus. This stimulus was sufficient to produce a startle reflex when given unexpectedly on its own. 3. The startling stimulus almost halved the latency of the voluntary response but did not change the configuration of the EMG pattern in either the arm or the leg. In some subjects the reaction times were shorter than the calculated minimum time for processing of sensory information at the cerebral cortex. Most subjects reported that the very rapid responses were produced by something other than their own will. 4. We conclude that the very short reaction times were not produced by an early startle reflex adding on to a later voluntary response. This would have changed the form of the EMG pattern associated with the voluntary response. Instead, we suggest that such rapid reactions were triggered entirely by activity at subcortical levels, probably involving the startle circuit. 5. The implication is that instructions for voluntary movement can in some circumstances be stored and released from subcortical structures.

Differentiation dependent expression in muscle cells of ZT3, a novel zinc finger factor differentially expressed in embryonic and adult tissues.

ZT3, isolated from a murine muscle cell cDNA library by a low-stringency hybridization, encodes a zinc finger domain containing factor with a transcript of 5.0 kb. A 3' 2.5 kb partial nucleotide sequence contains an ORF of 1.5 kb where 17 canonical C2H2 zinc finger domains organized in tandem were identified. It maps on mouse chromosome 11, close to two mutations which affect skeletal formation. ZT3 expression depends upon differentiation of myogenic cells in culture, since it is upregulated with myogenin and inhibited in scr-transfected C2C12 cells. ZT3 is not expressed in NIH3T3 or C3H10T1/2 fibroblasts, but is induced when fibroblasts are myogenically converted by transfection with the muscle regulatory genes (MRFs). Its expression is also upregulated in the rhabdomyosarcoma cell line RD induced to myogenic differentiation by TPA treatment. In postimplantation embryos, ZT3 is diffusely expressed but higher expression is detectable in the neural tube and encephalic vesicles, in the somites and, at a high level, in the limb buds as they form. During further development ZT3 is expressed in many tissues of neuroectodermal and mesodermal origin, but its expression decreases during fetal development and in the adult it is restricted to skeletal and cardiac muscle and to spleen. This pattern of expression suggests a possible role played by ZT3 in differentiating skeletal muscle. Its expression in other tissues is compatible with the suggestion that members of this class of DNA-binding factors play different roles during post-implantation development and in the adult life.

A muscle cell line from dystrophic mice expressing an altered phenotype in vitro.

The isolation and characterization of a myogenic cell line from C57BL/6J/dydy mice is described. This line (DyA4) maintains the morphological, biochemical and electrophysiological characteristics of the primary cultured cells, at least for 20 passages. The cells actively divide as long as they are subcultured in media supplemented with horse serum and embryo extract. If the cells are not subcultured for a few days, they fuse into multinucleated contracting myotubes, which readily synthesize specific muscle products such as acetylcholinesterase and acetylcholine receptor. This dystrophic cell line expresses in vitro the same altered phenotype that is characteristic of dystrophic muscle cells in primary cultures, namely reduced acetylcholine sensitivity and reduced acetylcholine receptor expression. Because they can be grown in large amounts, and represent a pure muscle cell population which express an altered phenotype in an in vitro aneural avascular environment, DyA4 cells provide a very useful model system for investigating the pathogenesis of murine muscular dystrophy.