Metaplasticity of the human trigeminal blink reflex

Although synaptic plasticity in the human cerebral cortex is governed by metaplasticity, whether a similar mechanism operates at brainstem level is unknown. In this study in healthy humans we examined the effects and interactions induced by pairing supraorbital nerve high-frequency electrical stimulation (HFS) protocols on the R2 component of the trigeminal blink reflex [Mao, J.B. & Evinger, C (2001) J Neurosci., 21:RC151(1-4)]. Changes in the R2 component were tested by pairing three different priming stimulation protocols inducing long-term potentiation (LTP)-like or long-term depression (LTD)-like effects (LTP-HFS and LTD-HFS), or no change (CONTROL-HFS) with a subsequent test LTP-HFS. Additionally, to examine changes in the R2 component induced by nonspecific factors, two CONTROL-HFS sessions were paired. Priming LTP-, LTD- or CONTROL-HFS potentiated, inhibited or left unchanged the area of the R2 component. Regardless of the type of priming LTP-, LTD- or CONTROL-HFS, the test LTP-HFS induced negligible differences in the R2 component. When two CONTROL-HFS sessions were paired, the test CONTROL-HFS increased the latency and markedly reduced the duration and area of the R2 component. The analysis of the normalized data across the first three experimental sessions, corrected for the inhibitory effects found in the fourth experiment, showed that the test LTP-HFS potentiated the R2 component area of the trigeminal blink reflex only when preceded by a priming LTD-HFS. We propose that homosynaptic metaplasticity might operate in the brainstem circuitry of the blink reflex.     

GLT-1 upregulation impairs prepulse inhibition of the startle reflex in adult rats

We tested the hypothesis that glutamate transporter GLT-1 (also known as EAAT2) plays a role in the regulation of prepulse inhibition (PPI) of the acoustic startle reflex, a simple form of information processing which is reduced in schizophrenia. To do this, we studied PPI in rats treated with ceftriaxone (200 mg/kg/day for 8 days), an antibiotic that selectively enhances GLT-1 expression and activity. We showed that ceftriaxone-induced GLT-1 upregulation is associated with impaired PPI of the startle, that this effect is reversed by dihydrokainate, a GLT-1 antagonist, that GLT-1 expression correlates negatively with PPI, and that PPI normalizes when GLT-1a levels return to baseline. Our data indicate that GLT-1 regulates PPI of the startle reflex.     

Hippocampal long‐term potentiation that is elicited by perforant path stimulation or that occurs in conjunction with spatial learning is tightly controlled by beta‐adrenoreceptors and the locus coeruleus

The noradrenergic system, driven by locus coeruleus (LC) activation, plays a key role in the regulating and directing of changes in hippocampal synaptic efficacy. The LC releases noradrenaline in response to novel experience and LC activation leads to an enhancement of hippocampus‐based learning, and facilitates synaptic plasticity in the form of long‐term depression (LTD) and long‐term potentiation (LTP) that occur in association with spatial learning. The predominant receptor for mediating these effects is the β‐adrenoreceptor. Interestingly, the dependency of synaptic plasticity on this receptor is different in the hippocampal subfields whereby in the CA1 in vivo, LTP, but not LTD requires β‐adrenoreceptor activation, whereas in the mossy fiber synapse LTP and LTD do not depend on this receptor. By contrast, synaptic plasticity that is facilitated by spatial learning is highly dependent on β‐adrenoreceptor activation in both hippocampal subfields. Here, we explored whether LTP induced by perforant‐path (pp) stimulation in vivo or that is facilitated by spatial learning depends on β‐adrenoreceptors. We found that under both LTP conditions, antagonising the receptors disabled the persistence of LTP. β‐adrenoreceptor‐antagonism also prevented spatial learning. Strikingly, activation of the LC before high‐frequency stimulation (HFS) of the pp prevented short‐term potentiation but not LTP, and LC stimulation after pp‐HFS‐induced depotentiation of LTP. This depotentiation was prevented by β‐adrenoreceptor‐antagonism. These data suggest that β‐adrenoreceptor‐activation, resulting from noradrenaline release from the LC during enhanced arousal and learning, comprises a mechanism whereby the duration and degree of LTP is regulated and fine tuned. This may serve to optimize the creation of a spatial memory engram by means of LTP and LTD. This process can be expected to support the special role of the dentate gyrus as a crucial subregional locus for detecting and processing novelty within the hippocampus. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

The effects of intra‐hippocampal L‐thyroxine infusion on long‐term potentiation and long‐term depression: A possible role for the αvβ3 integrin receptor

Although the effects of long‐term experimental dysthyroidism on long‐term potentiation (LTP) and long‐term depression (LTD) have been documented, the relationship between LTP/LTD and acute administration of L‐thyroxine (T4) has not been described. Here, we investigated the effects of intra‐hippocampal administration of T4 on synaptic plasticity in the dentate gyrus of the hippocampal formation. After a 15‐minute baseline recording, LTP and LTD were induced by application of high‐ and low‐frequency stimulation protocols, respectively. Infusions of saline or T4 and tetraiodothyroacetic acid (tetrac), a T4 analog that inhibits binding of iodothyronines to the integrin αvβ3 receptor, either alone or together, were made during the stimulation protocols. The averages of the excitatory postsynaptic potential (EPSP) slopes and population spike (PS) amplitudes, between 55 to 60 minutes, were used as a measure of the LTP/LTD magnitude and were analyzed by two‐way univariate ANOVA with T4 and tetrac as between‐subjects factors. The input–output curves of the infusion groups were comparable to each other, as shown by the non significant interaction observed between stimulus intensity and infused drug. The magnitude of the LTP in T4‐infused rats was significantly lower as compared to saline‐infused rats. Both the PS amplitude and the EPSP slope were depressed more markedly with T4 infusion than with saline, tetrac, and T4 + tetrac infusion. Data of this study provide in vivo evidence that T4 can promote LTD over LTP via the integrin αvβ3 receptor, and that the effect of endogenous T4 on this receptor can be suppressed by tetrac in the hippocampus. © 2016 Wiley Periodicals, Inc.     

Differential roles of basolateral and central amygdala on the effects of uncontrollable stress on hippocampal synaptic plasticity

The amygdala is considered central in mediating stress-related changes of hippocampal functions. However, it remains unclear whether different amygdala subnuclei have different roles in coordinating stress effects. Here, we report that stress exposure caused an immediate increase of extracellular signal-regulated kinase (ERK)1/2 phosphorylation in the hippocampal area CA1 and the basolateral amygdala (BLA) and after a delay in the central amygdala (CEA). Exposure to the novel environment following stress increased ERK1/2 phosphorylation in the CEA, but reversed the stress-induced increase of ERK1/2 phosphorylation in the hippocampal area CA1 and the BLA. Either ERK1/2 inhibitor U0126 or N-methyl-D-aspartate (NMDA) receptor antagonist DL-(-)-2-amino-5-phosphonopentanoic acid (APV) administration into the BLA, but not the CEA, blocked the stress effects on hippocampal long-term potentiation (LTP) and long-term depression. Novelty-exploration-induced reversal of stress effects was prevented when animals were injected U0126 or APV into the CEA, but not the BLA, before subjected to the novel environment. The ability of novelty exploration to reverse the stress effects was mimicked by intra-CEA infusion of NMDA. These findings suggest that BLA ERK1/2 signaling pathway is critical to mediate the stress effects on hippocampal synaptic plasticity; the activation of CEA ERK1/2, in contrast, appears to mediate the reversal of stress effects.     

Alterations in the balance of protein kinase and phosphatase activities and age-related impairments of synaptic transmission and long-term potentiation

Aging is associated with an impaired ability to maintain long-term potentiation (LTP), but the underlying cause of the impairment remains unclear. To gain a better understanding of the cellular and molecular mechanisms responsible for this impairment, the synaptic transmission and plasticity were studied in the CA1 region of hippocampal slices from adult (6-8 months) and poor-memory (PM)-aged (23-24 months) rats. The one-way inhibitory avoidance learning task was used as the behavioral paradigm to screen PM-aged rats. With intracellular recordings, CA1 neurons of PM-aged rats exhibited a more hyperpolarized resting membrane potential, reduced input resistance, and increased amplitude of afterhyperpolarization and spike threshold, compared with those in adult rats. Although a reduction in the size of excitatory synaptic response was observed in PM-aged rats, no obvious differences were found between adult and PM-aged rats in the pharmacological properties of excitatory synaptic response, paired-pulse facilitation, or frequency-dependent facilitation, which was tested with trains of 10 pulses at 1, 5, and 10 Hz. Slices from the PM-aged rats displayed significantly reduced early-phase long-term potentiation (E-LTP) and late-phase LTP (L-LTP), and the entire frequency-response curve of LTP and LTD is modified to favor LTD induction. The susceptibility of time-dependent reversal of LTP by low-frequency afferent stimulation was also facilitated in PM-aged rats. Bath application of the protein phosphatase inhibitor, calyculin A, enhanced synaptic response in slices from PM-aged, but not adult, rats. In contrast, application of the cAMP-dependent protein kinase inhibitors, Rp-8-CPT-cAMPS and KT5720, induced a decrease in synaptic transmission only in slices from the adult rats. Furthermore, the selective beta-adrenergic receptor agonist, isoproterenol, and pertussis toxin-sensitive G-protein inhibitor, N-ethylmaleimide, effectively restored the deficit in E-LTP and L-LTP of PM-aged rats. These results demonstrate that age-related impairments of synaptic transmission and LTP may result from alterations in the balance of protein kinase/phosphatase activities.     

Medial and lateral perforant path evoked potentials are selectively modulated by pairing with glutamatergic activation of locus coeruleus in the dentate gyrus of the anesthetized rat

Norepinephrine (NE) in vitro produces long-lasting potentiation of medial perforant path input and depression of lateral perforant path input to dentate gyrus in the rat. Similar, but highly transient, effects have been reported in vivo using paragigantocellular stimulation to release NE. The present study uses alternate stimulation of the medial perforant path and lateral olfactory tract (eliciting a lateral perforant path-evoked potential) to examine the effects of glutamatergic activation of locus coeruleus (LC) on the two pathways for up to 3 h post-LC activation. In the first experiment, the expected potentiation of the medial perforant path population spike in dentate gyrus was observed, but without accompanying depression of the lateral perforant path-mediated evoked potential (lateral olfactory tract stimulation, 60 s ISI). In a second experiment, with more frequent pairing of input with NE release (10 s ISI), significant potentiation of lateral perforant path-mediated input to dentate gyrus occurred, but potentiation of medial perforant path input was not seen. A third experiment with a 30 s ISI again produced potentiation of lateral perforant path-mediated input without potentiation of the medial perforant path population spike. The size of effects with the 30 s ISI was intermediate between that seen with 10 s and 60 s ISI. Potentiation of lateral perforant path over medial perforant path input has previously been reported with acute nicotinic activation of the LC. This outcome also resembles heterosynaptic modulation previously reported with tetanic potentiation. The data argue for a competitive relationship between medial and lateral perforant path inputs to dentate gyrus and suggest pairing with increased NE produces a bias favoring one or the other pathway depending on parameters such as strength and frequency. NE potentiating effects on lateral perforant path input here may also have occurred in entorhinal cortex (EC) given the system-wide NE release with LC activation.     

Dissociative identity disorder and prepulse inhibition of the acoustic startle reflex

A group of persons with dissociative identity disorder (DID) was compared with a group of persons with other dissociative disorders, and a group of nondiagnosed controls with regard to prepulse inhibition (PPI) of the acoustic startle reflex. The findings suggest maladaptive attentional processes at a controlled level, but not at a preattentive automatic level, in persons with DID. The prepulse occupied more controlled attentional resources in the DID group compared with the other two groups. Preattentive automatic processing, on the other hand, was normal in the DID group. Moreover, startle reflexes did not habituate in the DID group. In conclusion, increased PPI and delayed habituation is consistent with increased vigilance in individuals with DID. The present findings of reduced habituation of startle reflexes and increased PPI in persons with DID suggest the operation of a voluntary process that directs attention away from unpleasant or threatening stimuli. Aberrant voluntary attentional processes may thus be a defining characteristic in DID.     

Impact of contextual cues in the expression of the memory associated with diazepam withdrawal: involvement of hippocampal PKMζin vivo,and Arc expression and LTP in vitro

Hippocampal synaptic plasticity has been related to learning and adaptive processes developed during chronic drug administration, suggesting the existence of a common neurobiological mechanism mediating drug addiction and memory. Moreover, protein kinase M zeta (PKMζ) is critical for the maintenance of hippocampal long‐term potentiation (LTP) and spatial conditioned long‐term memories. Also, a link between activity‐regulated cytoskeleton‐associated protein (Arc), PKMζ and LTP has been proposed. Our previous results demonstrated that re‐exposure to the withdrawal environment was able to evoke the memory acquired when the anxiety measured as a diazepam (DZ) withdrawal sign was experienced. In the present work we evaluated if the memory associated with DZ withdrawal could be affected by changes in the contextual cues presented during withdrawal and by intrahippocampal administration of a PKMζ inhibitor. We found that the context was relevant for the expression of withdrawal signs as changes in contextual cues prevented the expression of the anxiety‐like behavior observed during plus‐maze (PM) re‐exposure, the associated enhanced synaptic plasticity and the increase in Arc expression. Furthermore, intrahippocampal administration of PKMζ inhibitor previous to re‐exposure to the PM test also impaired expression of anxiety‐like behavior and the facilitated LTP. These results support the relevance of the hippocampal synaptic plasticity in the maintenance of the memory trace during benzodiazepines withdrawal, adding new evidences for common mechanisms between memory and drug addiction that can be intervened for treatment or prevention of this pathology.     

Increased extracellular release of hippocampal NE is associated with tetanization of the medial perforant pathway in the freely moving adult male rat.

The induction of long-term potentiation (LTP) within the dentate gyrus of the hippocampal formation is modulated by many afferent influences from a number of subcortical structures known to be intimately involved in hippocampal-dependent learning and memory. It has been demonstrated in slice and anesthetized preparations that norepinephrine (NE) is one of these major neuromodulators involved in the induction of LTP. However, the majority of these studies have not been conducted in the freely moving animal. Recently, we developed surgical procedures and instrumentation techniques to simultaneously record electrophysiological and neurochemical data from the hippocampal formation. The present study uses these techniques to examine the underlying neurochemical changes in the hippocampus associated with the induction of hippocampal dentate LTP in the freely moving adult rat. These findings establish baseline levels of NE that can be used to evaluate the impact of various tetanization paradigms as well as the effect of a variety of insults on hippocampal plasticity.     

Functional dissociation between serotonergic pathways in dorsal and ventral hippocampus in psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition in rats

Altered hippocampal function and brain serotonin activity are implicated in the development and symptoms of schizophrenia. We have previously shown that lesions of the median raphe nucleus, but not the dorsal raphe nucleus, produced a marked enhancement of locomotor hyperactivity induced by phencyclidine and disruption of prepulse inhibition. The dorsal and ventral hippocampus receive serotonin projections predominantly from the median raphe nucleus and dorsal raphe nucleus, respectively. Therefore, we investigated the effect of local lesions of serotonin projections into the dorsal and ventral hippocampus on psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition. Male Sprague-Dawley rats were anaesthetized with pentobarbitone and stereotaxically microinjected with 5 microg of the serotonergic neurotoxin 5,7-dihydroxytryptamine into either the dorsal or the ventral hippocampus. Two weeks after surgery, dorsal hippocampus-lesioned rats showed a 100% enhancement of the locomotor hyperactivity caused by phencyclidine treatment and a slight but significant reduction of the effect of amphetamine. Prepulse inhibition was significantly disrupted in lesioned rats and serotonin levels in the dorsal hippocampus were reduced by 80%. Rats with lesions of the ventral hippocampus showed 85% depletion of serotonin and partial disruption of prepulse inhibition, but no significant changes in the effect of phencyclidine or amphetamine. These results suggest that serotonin projections from the median raphe nucleus to the dorsal hippocampus play an important role in locomotor hyperactivity and prepulse inhibition in rats, animal models of aspects of schizophrenia. This suggests that these serotonin projections may be involved in the pathophysiology of schizophrenia symptomology.     

Priming stimulation modifies synaptic plasticity in the perforant path of hippocampal slice in rat

Objective The potential of all central nervous system synapses to exhibit long term potentiation （LTP） or long term depression （LTD） is subject to modulation by prior synaptic activity, a higher-order form of plasticity that has been termed metaplasticity. This study is designed to examine the plasticity and metaplasticity in the lateral perforant path of rat. Methods Field potential was measured with different priming and conditioning stimulation protocols. Results Ten-hertz priming, which does not affect basal synaptic transmission, caused a dramatic reduction in subsequent LTP at lateral perforant path synapses in vitro, and the reduced LTP lasted for at least 2 h. The LTD was unaffected. The reduction of LTP in the lateral perforant path was also readily induced by applying priming antidromically at the mossy fibers. Conclusion Priming with 10 Hz, which is within a frequency range observed during physiological activity, can cause potent, long-lasting inhibition of LTP, but not LTD. This form of metaplasticity adds a layer of complexity to the activity-dependent modification of synapses within the dentate gyrus.     

Priming stimulation modifies synaptic plasticity in the perforant path of hippocampal slice in rat

1 Introduction The ability to modify synaptic strength in an activity- dependent manner, either as long-term depression (LTD) or as long-term potentiation (LTP) is a fundamental feature of most central nervous system synapses. The properties of different forms of LTP in the rodent hippocampus have been exceedingly well studied. A less well studied but par- ticularly intriguing finding is that the capacity of many syn- apses for plastic changes itself is subject to modulation of subsequent …     

A neural network approach to the acoustic startle reflex and prepulse inhibition

Prepulse inhibition (PPI) is the normal suppression of the startle reflex when an intense stimulus is preceded by a weak non-startling prestimulus. PPI is widely used as a model for sensorimotor gating processes and has been shown to be impaired in various neuropsychiatric disorders, including schizophrenia. We have reproduced startle-like behavior and basic PPI modifications with a neural network. The network design was constrained by the attempt (1) to use as few connections as possible and (2) to relate neuroanatomical structures to the simulated network. Performance of the network was evaluated by the behavior of the simulated motor neurons in response to prepulse and pulse stimuli presented with various lead intervals and prepulse intensities. A delayed inhibitory pathway via the pedunculopontine nucleus (PPTg) to the caudal pontine reticular nucleus was found to be a necessary but insufficient requirement to reproduce basic PPI output patterns. Additional requirements included (a) a low threshold at or below the caudal pontine reticular formation, (b) signal amplification in the inhibitory pathway and (c) prolongation of activity in the inhibitory pathway. On the grounds of the most appropriate output patterns of the simulations, we propose a mechanism of sustained activation in the PPTg due to recursive connections. Relations between stimuli, behavior (motor output) and the underlying architecture are discussed. Potentially, this modeling technique can be extended to investigate the impact of drugs and higher brain regions on PPI.     

Experimental hypothyroidism delays field excitatory post-synaptic potentials and disrupts hippocampal long-term potentiation in the dentate gyrus of hippocampal formation and Y-maze performance in adult rats

Manipulations of thyroid hormones have been shown to influence learning and memory. Although a large body of literature is available on the effect of thyroid hormone deficiency on learning and memory functions during the developmental stage, electrophysiological and behavioural findings, particularly on propylthiouracil administration to adult normothyroid animals, are not satisfactory. The experiments in the present study were carried out on 12 adult male Wistar rats aged 6-7 months. Hypothyroidism was induced by administering 6-n-propyl-2-thiouracil in their drinking water for 21 days at a concentration of 0.05%. The spatial learning performance of hypothyroid and control rats was studied on a Y-maze. The rats were then placed in a stereotaxic frame under urethane anaesthesia. A bipolar tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted into the granule cell layer of the ipsilateral dentate gyrus to record field excitatory post-synaptic potentials. After a 15-min baseline recording of field potentials, long-term potentiation was induced by four sets of tetanic trains. The propylthiouracil-treated rats showed a significantly attenuated input-output (I/O) relationship when population spike (PS) amplitudes and field excitatory post-synaptic potentials (fEPSP) were compared. fEPSP and PS latencies were found to be longer in the hypothyroid group than in the control group. The PS amplitude and fEPSP slope potentiations in the hypothyroid rats were not statistically different from those in the control rats, except for the field EPSP slope measured in the post-tetanic and maintenance phases. The hypothyroid rats also showed lower thyroxine levels and poor performance in the spatial memory task. The present study provides in vivo evidence for the action of propylthiouracil leading to impaired synaptic plasticity, which might explain deficit in spatial memory tasks in adult hypothyroid rats.     

Effects of unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm on synaptic plasticity in the hippocampal CA1 area in vivo

Repeated vivid recalls or flashbacks of traumatic memories and memory deficits are the cardinal features of post-traumatic stress disorder (PTSD). The underlying mechanisms are not fully understood yet. Here, we examined the effects of very strong fear conditioning (20 pairings of a light with a 1.5-mA, 0.5-s foot shock) and subsequent reexposure to the conditioning context (chamber A), a similar context (chamber B), and/or to the fear conditioned stimulus (CS) (a light) on synaptic plasticity in the hippocampal CA1 area in anesthetized Sprague-Dawley rats. The conditioning procedure resulted in very strong conditioned fear, as reflected by high levels of persistent freezing, to both the contexts and to the CS, 24 h after fear conditioning. The induction of long-term potentiation (LTP) was blocked immediately after fear conditioning. It was still markedly impaired 24 h after fear conditioning; reexposure to the conditioning chamber A (CA) or to a similar chamber B (CB) did not affect the impairment. However, presentation of the CS in the CA exacerbated the impairment of LTP, whereas the CS presentation in a CB ameliorated the impairment so that LTP induction did not differ from that of control groups. The induction of long-term depression (LTD) was facilitated immediately, but not 24 h, after fear conditioning. Only reexposure to the CS in the CA, but not reexposure to either chamber A or B alone, or the CS in chamber B, 24 h after conditioning, reinstated the facilitation of LTD induction. These data demonstrate that unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm can have profound effects on hippocampal synaptic plasticity, which may aid to understand the mechanisms underlying impairments of hippocampus-dependent memory by stress or in PTSD.     

Enriched environment exposure regulates excitability, synaptic transmission, and LTP in the dentate gyrus of freely moving rats

Performance in hippocampus-dependent and other tasks can be improved by exposure to an enriched environment (EE), but the physiological changes in neural function that may mediate these effects are poorly understood. To date, there have been conflicting reports regarding potential mechanisms, such as an increase in basal synaptic transmission, an increase in cell excitability, or altered synaptic plasticity. Here, we reexamined in freely moving animals the conditions under which varying degrees of EE exposure might lead to increases in synaptic or neural function in the dentate gyrus of the hippocampus. Adult male Sprague-Dawley rats were chronically implanted with stimulating and recording electrodes in the perforant path and dentate gyrus, respectively, and housed singly in standard cages. After stable recordings were established for field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs), the effects of various degrees of periodic novel environment exposure for 19 days were assessed. Exposure to an EE increased fEPSPs, but only when animals were kept in nominally low-stress housing conditions. An increase in granule-cell excitability, as evidenced by PS increases, was induced by all environmental treatments with the greatest effect being induced by overnight EE exposure. EE exposure did not change the level of long-term potentiation (LTP) induced by a moderate high-frequency tetanus, but continued EE exposure post-tetanus produced a significantly faster decay of LTP relative to control animals. These results suggest that, in adult animals, EE exposure may augment hippocampal information processing, but may also speed turnover of information in the hippocampus during the maintenance period.     

Neurophysiology of nocturnal enuresis: evoked potentials and prepulse inhibition of the startle reflex

Nocturnal enuresis is a genetically determined maturational disorder of the central nervous system. Lack of arousal and an inhibition deficit of the micturition reflex have been found as the main dysfunctions leading to wetting during sleep. Both are mediated by nuclei in the brainstem. Therefore, evoked potentials (brainstem auditory evoked potential [BAEP], visual evoked potential [VEP], event-related late acoustic-evoked potential [P300]), and the prepulse inhibition (PPI) of the startle reflex were assessed to further evaluate the brainstem deficit compared with cortical function. Thirty-seven children with nocturnal enuresis, aged 8 years to 14 years 8 months (mean age 10y 7mo [SD 1y 10mo]; 27 males, 10 females) were compared with 40 controls (mean age 10y 7mo [SD 1y 6mo]; 17 males, 23 females). Left interpeak latencies I-III and I-V of the BAEP were increased in children with nocturnal enuresis. VEP measures did not differ between patients and controls. However, children with a positive family history of enuresis showed a shorter latency towards N75 and P100 than children without such a family history. P300 and PPI measures did not differ. We conclude that this strongly supports the postulation of a maturational deficit of the brainstem in nocturnal enuretic children. The increased interpeak latencies I-III and I-V of the BAEP support the hypothesis of an arousal deficit mediated by delayed maturation of brainstem function. Differences in VEP latencies might point towards functional cortical differences in children with a family history of nocturnal enuresis.     

Azimuthal directional sensitivity of prepulse inhibition of the pinna startle reflex in decerebrate rats

Previous studies have indicated that the auditory midbrain, the inferior colliculus, is important for both sound localization and mediation of prepulse inhibition of the startle reflex. The present study investigated the azimuthal directional sensitivity of prepulse inhibition of the pinna startle reflex in decerebrate rats. The pinna startle reflex was measured by recording multi-unit action potentials from the cervicoauricular muscles. The startling noise burst (94 dB SPL) was produced by a stationary speaker at 0 degrees azimuth, and the non-startling prepulse noise burst (46 dB SPL) was produced by a movable speaker whose direction was changed in the frontal azimuthal plane. The interval between the onset of the prepulse sound and the onset of the startling sound was 100 ms. The pinna reflex to the startling sound was strongly inhibited by the prepulse sound, and the inhibited startle response exhibited a flat azimuthal directional curve. In addition to further confirming that the neural pathways mediating prepulse inhibition are located in the brainstem, the present results indicate that interaural disparities of binaural inputs used for sound localization are not capable of modulating prepulse inhibition of the startle reflex.     

Stability of the acoustic startle reflex, prepulse inhibition, and habituation in schizophrenia

Prepulse inhibition (PPI) of the acoustic startle reflex has been proposed as a neurophysiological measure of sensorimotor gating. There is high test-retest reliability of both startle magnitude and PPI in non-psychiatric subjects. The present study examined the stability of the acoustic startle reflex and its modulation in patients with schizophrenia. Startle measurements were performed in 19 chronic schizophrenic patients on stable medications and 24 healthy control subjects, three times at one-month intervals. PPI trials with various intervals between the prepulse and the startle stimulus (30, 60. 120, 240, and 2000 ms) were used. Intraclass correlation coefficients (ICC) were computed to assess stability. There was a good test-retest reliability of PPI in both schizophrenic patients (Mean ICC: 0.75) and control subjects (Mean ICC: 0.71). Acoustic startle magnitude was the most stable measure across sessions (Mean ICC schizophrenics: 0.89; Mean ICC controls: 0.89). In both groups, a good test-retest reliability was found in the startle latencies. Habituation and prepulse-induced shortening of latencies exhibited moderate stability. Schizophrenic patients exhibited significantly less PPI than control subjects in the 60 ms prepulse condition. This PPI deficit was evident in all three sessions. These results indicate that PPI is a stable neurobehavioral measure in chronic schizophrenic patients in the absence of changes in clinical state.