Prepulse Stimulation Research Articles

Maximal Fusion Capacity and Efficient Replenishment of the Dense Core Vesicle Pool in Hippocampal Neurons.

Neuropeptides and neurotrophins, stored in dense core vesicles (DCVs), are together the largest currently known group of chemical signals in the brain. Exocytosis of DCVs requires high-frequency or patterned stimulation, but the determinants to reach maximal fusion capacity and for efficient replenishment of released DCVs are unknown. Here, we systematically studied fusion of DCV with single vesicle resolution on different stimulation patterns in mammalian CNS neurons. We show that tetanic stimulation trains of 50-Hz action potential (AP) bursts maximized DCV fusion, with significantly fewer fusion event during later bursts of the train. This difference was omitted by introduction of interburst intervals but did not increase total DCV fusion. Interburst intervals as short as 5 s were sufficient to restore the fusion capacity. Theta burst stimulation (TBS) triggered less DCV fusion than tetanic stimulation, but a similar fusion efficiency per AP. Prepulse stimulation did not alter this. However, low-frequency stimulation (4 Hz) intermitted with fast ripple stimulation (200 APs at 200 Hz) produced substantial DCV fusion, albeit not as much as tetanic stimulation. Finally, individual fusion events had longer durations with more intense stimulation. These data indicate that trains of 50-Hz AP stimulation patterns triggered DCV exocytosis most efficiently and more intense stimulation promotes longer DCV fusion pore openings.SIGNIFICANCE STATEMENT Neuropeptides and neurotrophins modulate multiple regulatory functions of human body like reproduction, food intake or mood. They are packed into dense core vesicles (DCVs) that undergo calcium and action potential (AP) fusion with the plasma membrane. In order to study the fusion of DCVs in vitro, techniques like perfusion with buffer containing high concentration of potassium or electric field stimulation are needed to trigger the exocytosis of DCVs. Here, we studied the relationship between DCVs fusion properties and different electric field stimulation patterns. We used six different stimulation patterns and showed that trains of 50-Hz action potential bursts triggered DCV exocytosis most efficiently and more intense stimulation promotes longer DCV fusion pore openings.

Results of balance tests and gait parameters are not dependent on each other in patients with balance problems

Prepulse inhibition (PPI) is a neurophysiological phenomenon whereby a weak stimulus modulates the reflex response to a subsequent strong stimulus. Its physiological purpose is to avoid interruption of sensory processing by subsequent disturbing stimuli at the subcortical level, thereby preventing undesired motor reactions. An important hub in the PPI circuit is the pedunculopontine nucleus, which is also involved in the control of posture and sleep/wakefulness.To study the effect of posture (supine versus standing) on PPI, induced by somatosensory prepulses to either upper or lower limb. PPI was measured as the percentage inhibition of the blink reflex response to electrical supraorbital nerve (SON) stimulation.Sixteen healthy volunteers underwent bilateral blink reflex recordings following SON stimulation either alone (baseline) or preceded by an electrical prepulse to the median nerve (MN) or sural nerve (SN), both in supine and standing. Stimulus intensity was 8 times sensory threshold for SON, and 2 times sensory threshold for MN and SN, respectively. Eight stimuli were applied in each condition.Baseline blink reflex parameters did not differ significantly between the two postures. Prepulse stimulation to MN and SN caused significant inhibition of R2. In supine but not in standing, R2 was significantly more inhibited by MN than by SN prepulses. In standing, SN stimulation caused significantly more inhibition of R2 than in supine, while the inhibition caused by MN prepulses did not differ significantly between postures.PPI induced by lower limb afferent input may contribute to postural control while standing.

The importance of a comprehensive assessment when tuning ankle-foot orthoses in cerebral palsy: a case report

Prepulse inhibition (PPI) is a neurophysiological phenomenon whereby a weak stimulus modulates the reflex response to a subsequent strong stimulus. Its physiological purpose is to avoid interruption of sensory processing by subsequent disturbing stimuli at the subcortical level, thereby preventing undesired motor reactions. An important hub in the PPI circuit is the pedunculopontine nucleus, which is also involved in the control of posture and sleep/wakefulness.To study the effect of posture (supine versus standing) on PPI, induced by somatosensory prepulses to either upper or lower limb. PPI was measured as the percentage inhibition of the blink reflex response to electrical supraorbital nerve (SON) stimulation.Sixteen healthy volunteers underwent bilateral blink reflex recordings following SON stimulation either alone (baseline) or preceded by an electrical prepulse to the median nerve (MN) or sural nerve (SN), both in supine and standing. Stimulus intensity was 8 times sensory threshold for SON, and 2 times sensory threshold for MN and SN, respectively. Eight stimuli were applied in each condition.Baseline blink reflex parameters did not differ significantly between the two postures. Prepulse stimulation to MN and SN caused significant inhibition of R2. In supine but not in standing, R2 was significantly more inhibited by MN than by SN prepulses. In standing, SN stimulation caused significantly more inhibition of R2 than in supine, while the inhibition caused by MN prepulses did not differ significantly between postures.PPI induced by lower limb afferent input may contribute to postural control while standing.

Influence of posture on blink reflex prepulse inhibition induced by somatosensory inputs from upper and lower limbs

BackgroundPrepulse inhibition (PPI) is a neurophysiological phenomenon whereby a weak stimulus modulates the reflex response to a subsequent strong stimulus. Its physiological purpose is to avoid interruption of sensory processing by subsequent disturbing stimuli at the subcortical level, thereby preventing undesired motor reactions. An important hub in the PPI circuit is the pedunculopontine nucleus, which is also involved in the control of posture and sleep/wakefulness. ObjectiveTo study the effect of posture (supine versus standing) on PPI, induced by somatosensory prepulses to either upper or lower limb. PPI was measured as the percentage inhibition of the blink reflex response to electrical supraorbital nerve (SON) stimulation. MethodsSixteen healthy volunteers underwent bilateral blink reflex recordings following SON stimulation either alone (baseline) or preceded by an electrical prepulse to the median nerve (MN) or sural nerve (SN), both in supine and standing. Stimulus intensity was 8 times sensory threshold for SON, and 2 times sensory threshold for MN and SN, respectively. Eight stimuli were applied in each condition. ResultsBaseline blink reflex parameters did not differ significantly between the two postures. Prepulse stimulation to MN and SN caused significant inhibition of R2. In supine but not in standing, R2 was significantly more inhibited by MN than by SN prepulses. In standing, SN stimulation caused significantly more inhibition of R2 than in supine, while the inhibition caused by MN prepulses did not differ significantly between postures. SignificancePPI induced by lower limb afferent input may contribute to postural control while standing.

BS19. Reorganization of sensory input in brainstem after peripheral facial paralysis

Peripheral facial nerve palsy (PFP) is characterized by reduced motor performance on one side of face. The electrophysiological findings show smaller or delayed motor and facial reflex responses. It leads to a cortical reorganization and an imbalance in sensorimotor gating is also likely since sensory pathways innervating facial structures are intact and sensory inputs to face are transmitted smoothly. Herein, we aimed to analyze the alterations in sensorimotor gating at the level of brainstem after PFP. To examine sensorimotor gating, we used prepulse modulation (PPM) of blink reflex (BR). We also recorded recovery (RC) of BR to identify excitability changes in the facial nucleus. We included 33 patients with PFP and 39 recordings in those patients. Six patients had serial recordings. Control group was composed of 16 healthy subjects with similar age and gender to the patient group (Table). Baseline BR, BR recovery at ISI of 300 ms and BR-PPM at ISI of 100 ms were performed on the right sides of healthy subjects and on both sides of patients. Severity of PFP was assessed according to clinical findings by House-Brackman scale and using electrophysiological methods. Patients with BR, facial motor response or electromyography findings indicating axon loss more than 85% were considered to have severe axon loss. Time lapse from the onset was categorized as early (<15 days), middle (12–45 days) and late (>45 days). R1, R2 and R2c components of BR on symptomatic side were absent in 17, 9 and 13 recordings, respectively. When they were recorded, latencies were longer and magnitude was lower over symptomatic sides of patients compared to healthy subjects or asymptomatic sides of patients. Multivariate ANOVA showed significance at group level, at prepulse level and group x prepulse level. Mean magnitude of R1 was increased whereas mean R2 and R2c magnitude were reduced in all groups after prepulse stimulation (prepulse inhibition, PPI). Interestingly, suppression of R2 or R2c was lower on both sides of patient group compared to healthy subjects. There was no association between PPM% and categories according to time lapse or HBs. PPM% did not correlate with time lapse, either. Although R2-RC and R2C-RC were lower in healthy subjects compared to both sides of patients, the difference was not significant. When we conducted a multivariate analysis between BR-RC with fixed factor time lapse and HB, recovery rates were significantly lower in patients with lower HB scores. Prepulse inhibition of R2 BR is reduced in patients with PFP. Filtering of facial sensory input at brainstem level is decreased leading to an increased transfer of trigeminal sensory inputs through brainstem. Although increased BR-RC correlated with disease severity, there was no correlation between reduced PPI-BR. Thus, reduced PPI is presumably related to monitor and to choose correct sequence of facial movements.

BS18. Reduced prepulse inhibition in trigeminal neuralgia

We hypothesized that prepulse inhibition (PPI) may be decreased in trigeminal neuralgia (TN) if it leads hyperactivity of trigeminal nucleus and tested our hypothesis in a group of patients with classical TN. Consecutive nine patients with classical TN and 14 healthy subjects were enrolled in this study between January 2015 and August 2016. Diagnosis and classification were done according to the International Classification of Headache Disorders-3 (ICHD-3 beta version). Blink reflex and BR-PPI were recorded on both symptomatic and asymptomatic sides in patient group and on the right side in healthy subjects. Subthreshold conditioning stimulus was applied to the median nerve at second finger using an electrical stimulus at two different interstimulus intervals: 50 ms and 100 ms before the test stimulus to the supraorbital nerve. Standard BR recordings were normal in all groups. In healthy subjects, prepulse stimulus resulted in lower magnitude of BR-R2 (p = 0.000) and longer R2 latencies (p = 0.008) at ISIs of 50 ms and 100 ms in comparison to baseline recordings whereas no change after prepulse stimulation was observed on both symptomatic and asymptomatic sides of patients with TN. Our study provided evidence for the reduced PPI and thus, sensory gating of brainstem in classical TN. This finding was bilateral and present even on the asymptomatic side.

Differential modulation of prepulse inhibition of the blink reflex in peripersonal versus extrapersonal space

Threatening stimuli encountered in peripersonal space (PPS) are processed differently from those encountered in extrapersonal space (EPS). This phenomenon is attributed to tonic top-down modulation. We hypothesized that prepulse inhibition (PPI) of a reflex, which has a protective function, may change according to whether the conditioning stimulus appears in PPS or EPS. We aimed to compare the strength of the PPI according to whether stimulation was delivered in PPS or EPS. The study included 23 healthy subjects with a mean age of 36.8±9.1years. Recordings of blink reflex (BR) after supraorbital stimulation (so-BR) were performed. Recordings of BR after prepulse stimulation to the median nerve 100ms prior to the supraorbital stimulation were acquired with the ipsilateral hand 50-60cm from the face (EPS) and approximately 3-4cm from the face (PPS). Changes of response magnitudes were compared between PPS and EPS conditions. R2 area-under-the curve of so-BR was reduced after prepulse stimulation of median nerve in all subjects while the hand was in EPS. Although the R2 magnitude was also decreased after prepulse stimulation while the hand was in PPS, the percentage of reduction with the hand in PPS was significantly smaller compared to that with the hand in EPS. Reduction in R2 magnitude after prepulse stimulation 100ms prior to test pulse is recognized (PPI). Although PPI was observed under both conditions, PPI of so-BR was attenuated when the stimulus was presented in the PPS. Therefore, our study provides evidence for modulation of PPI of so-BR in PPS and may suggest top-down modulation of the neural circuitry underlying PPI.

Reorganization of sensorimotor gating after peripheral facial palsy starts at brainstem

ABSTRACTBackground and objective We aimed to analyze the alterations in sensorimotor gating at brainstem after peripheral facial palsy (PFP). To examine sensorimotor gating, we used prepulse modulation (PPM) of blink reflex (BR). We also recorded BR recovery to identify excitability changes in the facial nucleus.Patients and method We included 33 patients and 39 recordings. Control group was composed of 16 healthy subjects. Simultaneous bilateral baseline BR, BR recovery at ISI of 300-ms and BR-PPM at ISI of 100-ms recordings were performed after stimulation of trigeminal nerve on right sides of healthy subjects and on both sides of patients. Severity of PFP and time lapse from the onset was noted.Results Mean R1 amplitude was increased, whereas mean R2 and R2c magnitude were reduced in all groups after prepulse stimulation. However, multivariate ANOVA showed significance at group level (patients and healthy subjects), at prepulse level (no prepulse and 100-ms prepulse) and group and prepulse level. Suppression of R2 or R2c was lower on both sides of patients compared to healthy subjects and the deficit first started on the symptomatic side.Conclusion Suppression of R2 and R2c after prepulse stimulation is reduced in PFP suggesting decreased filtering of facial sensory input at brainstem level. Trigeminal sensitization at brainstem develops early after PFP.

P244 Normal cortical modulation of subcortical structures is altered in cervical dystonia

Objective Blink reflex (BR) is obtained after different kinds of stimuli, such as trigeminal supraorbial branch stimulation (trigeminal BR, TBR) or median nerve stimulation at wrist (hand-evoked BR, HBR). Inhibition of TBR occurs when a preceding subthreshold stimulus is applied before trigeminal stimulation (prepulse inhibition, PPI). In healthy subjects, magnitude of HBR is increased and magnitude of PPI of TBR is decreased if the stimulated hand is positioned in the peripersonal space (PPS). Here, we aimed to investigate the changes of HBR and PPI of the TBR in PPS to understand alterations of cortical modulations of subcortical structures in cervical dystonia. Patients and method We recruited 23 consecutive patients with idiopathic CD and 21 healthy subjects. All participants had HBR and age and gender were similar between groups. HBR and PPI of the TBR were recorded while stimulated hand was in the extrapersonal space (far condition) and in the PPS (near condition). Baseline values were compared between patient with CD and healthy subjects. Further comparisons were done between far and near conditions. Results Magnitude of baseline HBR was bigger in patients with CD compared to healthy subjects. The magnitude further increased in healthy subjects whereas it was reduced in patients with CD. In healthy subjects, prepulse stimulation led to the reduced magnitude of R2 component of BR under far condition whereas the reduction was less evident under near condition. Although prepulse inhibition was low in patients with CD compared to healthy subjects, the reduction was more evident under near condition in patients with CD. Discussion Enhancement of HBR and attenuation of PPI of the TBR in the PPS is a normal phenomenon that provides evidence for top-down modulation of the neural circuitry underlying these reflexes. In CD, these normal alterations are lost which suggest abnormal modulation of higher-order centers.

Blink reflex prepulse inhibition and excitability recovery: Influence of age and sex

ObjectiveAge and sex affect various reflexes in healthy humans. Their respective influence on prepulse inhibition (PPI) of the trigeminofacial blink reflex (BR) and BR excitability recovery has not as yet been investigated in detail. MethodsWe studied the trigeminofacial BR bilaterally in 62 healthy volunteers (31 males, age 41.0±13.2years, mean±SD, 31 females, 39.2±11.7years) following right supraorbital nerve stimulation. Single sweeps were recorded either alone (n=8) or conditioned by a prepulse applied 100ms earlier to the dominant index finger though ring electrodes (n=8). Latency and amplitude of the ipsilateral R1 component, as well as latency and area-under-the-curve of the ipsilateral R2 and contralateral R2c components were measured in single traces and then averaged per subject. BR excitability recovery was established bilaterally following right supraorbital nerve stimulation with paired pulses. Six responses were averaged on-line per interstimulus interval (ISI 160, 300, and 500ms). ResultsUnconditioned BR did not differ significantly between males and females, but R2 and R2c latencies increased with age. Prepulse stimulation caused significant facilitation of R1 (latency and amplitude), and inhibition of R2 and R2c (latency and area), irrespective of age. PPI of R2 and R2c area was significantly more pronounced in men. BR excitability recovery was significantly influenced by age, but not by sex. Multiple regression showed inverse correlation of age with conditioned R2 and R2c area at ISI 300ms and 500ms (P<0.01 each), indicating reduced excitability recovery. No parameter showed significant interaction of age×sex. ConclusionThese data indicate less pronounced PPI of the trigeminofacial BR in females, concurring with previous reports of sex differences in protective reflexes, but also suggesting less rigorous filtering of information flow to the brain in females. Reduced BR excitability to paired-pulse stimulation may counteract age-related disinhibition of brainstem interneuronal circuitry. SignificanceThe present findings allow new insight into human brainstem physiology.

Narcolepsy–cataplexy: deficient prepulse inhibition of blink reflex suggests pedunculopontine involvement

Hypocretin (orexin) deficiency plays a major role in the pathophysiology of narcolepsy-cataplexy. In animal models, hypocretinergic projections to the pedunculopontine nucleus are directly involved in muscle tone regulation mediating muscle atonia - a hallmark of cataplexy. We hypothesized that pedunculopontine nucleus function, tested with prepulse inhibition of the blink reflex, is altered in human narcolepsy-cataplexy. Twenty patients with narcolepsy-cataplexy and 20 healthy controls underwent a neurophysiological study of pedunculopontine nucleus function. Blink reflex, prepulse inhibition of the blink reflex and blink reflex excitability recovery were measured. Blink reflex characteristics (R1 latency and amplitude, and R2 and R2c latency and area under the curve) did not differ between patients and controls (P > 0.05). Prepulse stimulation significantly increased R2 and R2c latencies and reduced R2 and R2c areas in patients and controls. However, the R2 and R2c area suppression was significantly less in patients than in controls (to 69.8 ± 14.4 and 74.9 ± 12.6%, respectively, versus 34.5 ± 28.6 and 43.3 ± 29.5%, respectively; each P < 0.001). Blink reflex excitability recovery, as measured by paired-pulse stimulation, which is not mediated via the pedunculopontine nucleus, did not differ between patients and controls (P > 0.05). Our data showed that prepulse inhibition is reduced in narcolepsy-cataplexy, whereas unconditioned blink reflex and its excitability recovery are normal. Because the pedunculopontine nucleus is important for prepulse inhibition, these results suggest its functional involvement in narcolepsy-cataplexy.

Neurophysiological evidence for muscle tone reduction by intrathecal baclofen at the brainstem level

Objective Intrathecal baclofen (ITB) is an efficient treatment modality for severe spasticity that is considered to act at the spinal level. Its influence on phasic spasticity is usually determined clinically by testing muscle reflexes, and on tonic spasticity by using scores such as the Modified Ashworth Scale (MAS). Neurophysiological techniques, e.g., soleus H reflex, may provide additional information regarding ITB efficacy. There is, however, only scarce information available on time–response relationships of clinical and neurophysiological measures of spasticity obtained at different levels along the neuroaxis. Methods Fourteen patients with severe spastic paraparesis underwent serial evaluation of MAS in upper and lower limbs and serial testing of H reflex in soleus and flexor carpi radialis muscles, T wave in quadriceps and biceps brachii muscles, and blink reflex (BR) with and without prepulse, at baseline, and 15, 30, 60, 90, 120, and 180 min following ITB bolus application. Results ITB bolus application caused significant suppression of soleus H reflex after 15 min and of quadriceps T wave after 30 min, while MAS dropped significantly after 60 min together with significant suppression of BR R2 area without and with prepulse stimulation. H reflex in flexor carpi radialis and T wave in biceps brachii were not significantly suppressed by ITB. The time course of early changes in soleus H max/ M max ratio and quadriceps T wave indicates a suppression of hyperreflexia at the spinal level, while a later reduction of MAS synchronously with suppression of BR with and without prepulse concurs with a brainstem effect of ITB. Conclusion Temporal concurrence between suppression of brainstem reflexes and desired suppression of lower limb muscle hypertonia after ITB bolus application suggests that both may be at least partially mediated from a common CNS region of activity. Significance Our data concur with a significant brainstem action of ITB.

The effect of a prepulse stimulus on the EMG rebound following the cutaneous silent period

The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by Adelta fibres. The postinhibitory rebound of electromyographic (EMG) activity following the CSP has been mainly attributed to resynchronization of motoneurons, but the possibility of startle reflex activity contributing to the EMG burst has also been suggested. Several types of reflexes may be suppressed by a preceding weak stimulus--a phenomenon called prepulse inhibition (PPI). Our aim was to study whether PPI would diminish the EMG rebound, thereby providing further evidence for excitatory reflex activity contained within the postinhibitory EMG rebound following the CSP. Ten healthy subjects underwent CSP testing following noxious digit II stimulation in two conditions, with and without a prepulse applied to digit III. Rectified surface EMG recordings were obtained from right orbicularis oculi, sternocleidomastoid and thenar muscles of the dominant hand during thumb abduction with 25% of maximum force. The area of the EMG rebound and the EMG reflex responses in orbicularis oculi and sternocleidomastoid were significantly smaller in recordings where a prepulse stimulus was applied 100 ms before the stimulus as compared to control responses without prepulse. CSP onset and end latency, CSP duration, and the degree of EMG suppression were not influenced. Prepulses significantly reduced subjective discomfort as based on visual analog scale scores. Inhibition of the EMG rebound by prepulse stimulation supports the hypothesis that the excitatory EMG activity following the CSP contains not only resynchronization of motoneuronal firing, but also an excitatory reflex component. The most probable type of reflex seems to be a somatosensory startle reflex, a defence reaction which is generated in structures located in the caudal brainstem following an unexpected intense stimulus. Reduction of the discomfort associated with high-intensity electrical fingertip stimulation by a prepulse without affecting CSP parameters underlines the utility of PPI in the context of CSP testing.

1.7. The effect of prepulse stimulation on the post-inhibition EMG rebound following the cutaneous silent period

1.7. The effect of prepulse stimulation on the post-inhibition EMG rebound following the cutaneous silent period

Potentiation of local field potentials in the anterior cingulate cortex evoked by the stimulation of the medial thalamic nuclei in rats

The limbic thalamus and cingulate cortex are essential components in mediating the affective component of pain responses. In the present study, we examined the excitatory properties of medial thalamus (MT)-evoked field potentials in the anterior cingulated cortex (ACC). We also examined the effects of paired pulses and brief tetanic stimuli of the MT. The aim of this study was to determine whether nociceptive inputs to medial thalamic afferents cause plastic changes in the ACC. In α-chloralose (50 mg/kg, i.v.) anaesthetized rats, tungsten microelectrodes were used to stimulate the MT and to record field potentials in the ACC. The locations of MT were identified by searching and examining their responses to peripheral noxious stimuli. Early negative (about 4.7 ms latency) and late positive (about 11.7 ms) potentials could be evoked in the ACC by MT stimuli. The evoked field potentials were potentiated by prepulse stimulation. Maximal paired pulse facilitation (509±51%) was produced in 80–150 ms interpulse intervals. Evoked field potentials were also potentiated (28.8±6.3% and 29.6±5.9%, respectively) by low (10 Hz/10 s) and high (100 Hz/2s/2×) frequency tetanic stimulation of the MT, with a duration maintained for about 90 s and 120 min, respectively. The potentiation of MT-evoked ACC potentials provides a neural basis for synaptic plasticity, which may be essential for the establishment of pain-initiated conditioning behavior and affective responses to noxious stimuli.

Selective Blockade of N‐Type Calcium Channels by Levetiracetam

We investigated the effect of the new antiepileptic drug (AED) levetiracetam (LEV) on different types of high-voltage-activated (HVA) Ca2+ channels in freshly isolated CA1 hippocampal neurons of rats. Patch-clamp recordings of HVA Ca2+ channel activity were obtained from isolated hippocampal CA1 neurons. LEV was applied by gravity flow from a pipette placed near the cell, and solution changes were made by electromicrovalves. Ca2+ channel blockers were used for separation of the channel subtypes. The currents were measured in controls and after application of 1-200 microM LEV. LEV irreversibly inhibited the HVA calcium current by approximately 18% on the average. With a prepulse stimulation protocol, which can eliminate direct inhibition of Ca2+ channels by G proteins, we found that G proteins were not involved in the pathways underlying the LEV inhibitory effect. This suggested that the inhibitory effect arises from a direct action of LEV on the channel molecule. The blocking mechanism of LEV was not related to changes in steady-state activation or inactivation of Ca2+ channels. LEV also did not influence the rundown of the HVA Ca2+ current during experimental protocols lasting approximately 10 min. Finally, LEV at the highest concentration used (200 microM) did not influence the activity of L-, P- or Q-type Ca2+ channels in CA1 neurons, while selectively influencing the activity of N-type calcium channels. The maximal effect on these channels separated from other channel types was approximately 37%. Our results provide evidence that LEV selectively inhibits N-type Ca2+ channels of CA1 pyramidal hippocampal neurons. These data suggest the existence of a subtype of N-type channels sensitive to LEV, which might be involved in the molecular basis of its antiepileptic action.

Development of the acoustic startle response in the rat: Ontogenetic changes in the magnitude of inhibition by prepulse stimulation

Three experiments examined the development of the acoustic startle reflex and its modification by a preliminary stimulus in the infant rat during the 2nd and 3rd postnatal weeks. The 1st experiment employed a white noise S1 (20 msec, 70 dB), the 2nd a cutaneous S1 (.5 msec, .5 mA and 1.0 mA shock), and the 3rd identical S1-S2 pairs (20 msec, 10 kHz, 110 dB tones). The results demonstrate a similar maturation of the prepulse modification pattern over days in the 3 experiments, evidenced mainly in the growth of inhibition. The findings indicate peripheral and central mechanisms that are maturing during the period of life under observation and that contribute to the developmental patterns of modification.