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D M Caspary

Publications and source records attributed to D M Caspary.

At least 55 records · Page 3Linked to original sources
PubMed1987

Strychnine alters the fusiform cell output from the dorsal cochlear nucleus.

Anatomical and physiological evidence suggests that fusiform cells, the major output neurons of the dorsal cochlear nucleus (DCN), receive significant inhibitory input. Fusiform cells often display strongly non-monotonic rate-intensity functions and pauser-buildup or buildup tone-evoked temporal responses, patterns which may be mediated by inhibitory neurotransmitters. Other neurons located within the fusiform cell layer or in the more superficial molecular layer display varied rate-intensity functions and temporal responses. Neurons displaying response properties characteristic of fusiform cells are sensitive to iontophoretic application of the inhibitory amino acid neurotransmitter, glycine. Application of the glycine receptor antagonist, strychnine, alters the non-monotonic portion of the rate-intensity function at doses which do not alter spontaneous activity or near-threshold tone-evoked responses. These neurons are also sensitive to GABA and the GABAB agonist, (-)-baclofen, but are insensitive to the GABAA antagonist, bicuculline. DCN neurons which display monotonic rate-intensity functions and temporal response properties different than those associated with fusiform cells are sensitive to bicuculline, (-)-baclofen, and GABA. These data suggest that a glycinergic input onto fusiform cells may control the non-monotonic nature of the response of these neurons near characteristic frequency and therefore may contribute significantly to the nature of the output of the DCN.

Acoustic Stimulation↗
PubMed1986

Inferior colliculus neuronal response abnormalities in genetically epilepsy-prone rats: evidence for a deficit of inhibition.

The genetically epilepsy-prone rat (GEPR) is abnormally susceptible to induction of seizures by acoustic stimulation. The inferior colliculus (IC) is critically important to audiogenic seizure susceptibility. The GEPR is more susceptible to induction of audiogenic seizures at 12 kHz than at other pure tone frequencies. IC neurons in the GEPR exhibit significantly elevated response thresholds and broader tuning characteristics than normal. These findings along with previous neurophysiological and anatomical data suggest that a hearing deficit occurs in the GEPR. IC neurons in the GEPR exhibit a significantly elevated incidence of a response pattern with a peak of activity at the beginning and end of the stimulus, the onset-offset response. This response pattern occurs at 12 kHz and at characteristic frequency with high stimulus intensities and may represent an afterdischarge phenomenon. The onset-offset pattern may be a manifestation of central mechanisms developed to compensate for reduced peripheral auditory input that appears to be involved in the hearing deficit of the GEPR. Such compensatory mechanisms may involve alterations of the actions of neurotransmitters of the brain-stem auditory nuclei. GABA is implicated as an inhibitory transmitter in the IC. Iontophoretic application of GABA or a benzodiazepine produces significantly less inhibition of IC neurons of the GEPR than of the normal rat. Endogenous sound-induced (binaural) inhibition which is suggested to be GABA-mediated is also significantly reduced in IC neurons of the GEPR. Iontophoresis of the GABAA antagonist, bicuculline, often converts normal response patterns in the IC to onset-offset responses seen with high incidence in GEPR IC neurons, suggesting that the decreased effectiveness of GABA may lead to the onset-offset prevalence. This reduced effectiveness of inhibition may be unable to compensate for the rise in the putative excitatory transmitter, aspartate, in IC during high intensity acoustic stimulation in the GEPR. These altered transmitter actions may be important mechanisms subserving initiation of audiogenic seizures in the genetically epilepsy-prone rat.

Acoustic Stimulation↗
PubMed1986

Neuronal response abnormalities in the inferior colliculus of the genetically epilepsy-prone rat.

The genetically epilepsy-prone (GEP) rat is susceptible to seizure induction by acoustic stimuli. The inferior colliculus (IC) has been implicated as being critically important in audiogenic seizure susceptibility based on lesion, electrical stimulation, and focal implantation experiments. The current study determined that GEP rats were most susceptible to seizure induction by pure tone bursts at 100 dB at a frequency of 12 kHz. IC neurons in the GEP rat exhibited a significantly elevated incidence of a particular response pattern at 12 kHz and at characteristic frequency. This pattern consisted of a peak at the beginning and end of the stimulus (onset-offset response). This response pattern only occurred with high intensity stimuli approximating those which induce seizures and may represent an afterdischarge phenomenon. The response threshold was significantly elevated and tuning characteristics were also significantly altered in IC neurons of GEP rats as compared to normal IC neurons. The latter two findings may be related to the deficit of hearing which is reported in the GEP rat. The increased incidence of onset-offset responses may be due to a decreased efficacy of inhibition in the GEP rat neurons as compared to normal rat neurons.

Acoustic Stimulation↗
PubMed1986

Decreased effectiveness of GABA-mediated inhibition in the inferior colliculus of the genetically epilepsy-prone rat.

The inferior colliculus (IC) is a critical site for induction of audiogenic seizures in the genetically epilepsy-prone rat (GEPR). Abnormal response properties observed in inferior colliculus neurons of that strain include a high incidence of onset-offset responses which may be a form of afterdischarge. These response abnormalities may involve altered actions of neurotransmitters in that region of the brain. GABA is implicated as a transmitter in endogenous sound-induced inhibition in the inferior colliculus. Endogenous inhibition and the actions of agents that affect GABA receptors were examined in inferior colliculus neurons in epileptic and normal rats. The iontophoretic dose (current) of GABA required to suppress neuronal firing in the epilepsy-prone rat was significantly greater than that required in neurons of the normal rat. A form of endogenous (binaural) inhibition in inferior colliculus neurons, which is proposed to be GABA-mediated, was also significantly reduced in the epilepsy-prone rat as compared with the normal rat. A benzodiazepine (flurazepam) which enhances the action of GABA in many brain sites including the inferior colliculus was significantly less effective than normal when applied iontophoretically onto the same neurons of the epilepsy-prone rat. The GABAA antagonist, bicuculline, which blocks the effect of GABA on inferior colliculus neurons, frequently induced the onset-offset response in neurons not previously exhibiting this pattern. These findings suggest that the reduction of GABA-mediated inhibition in the genetically epilepsy-prone rat may result in the increased incidence of afterdischarges in neurons of the inferior colliculus and may serve as an important mechanism of epileptogenesis in audiogenic seizures in this genetic form of epilepsy.

Animals↗
PubMed1985

Comparative effects of convulsant drugs on the sensory responses of neurons in the amygdala and brainstem reticular formation.

The sensory responses of neurons in the amygdala and mesencephalic reticular formation in the cat were enhanced following the intravenous administration of subconvulsant doses of bicuculline, strychnine, bemegride, pentylenetetrazol and physostigmine. The degree and intensity of the enhancement of the response was considerably greater in the reticular formation than in the amygdala. The latency of the response in simultaneously-recorded pairs of neurons in the amygdala and reticular formation was significantly shorter in the mesencephalic reticular formation. The enhancement induced by convulsants does not appear to be transmitter-specific, since enhancement was produced with sequential administration of convulsant drugs which affect gamma-aminobutyric acid (GABA), glycine or acetylcholine. These findings suggest that the reticular formation is involved, to a larger degree than the amygdala, in the ability of sensory stimuli to initiate generalized convulsive seizures in animals treated with these convulsant drugs. The enhancement of the response in the hippocampus and cortex, which has previously been shown to exhibit a longer latency and a lower degree of enhancement than the reticular formation, coupled with the findings in the amygdala, suggest that the reticular formation may mediate the enhancement of the response of these other regions of the brain. The spread of the enhancement of the response to other structures in the brain via the widely distributed output pathways from the reticular formation may lead to initiation of generalized seizures by a recruitment-like process, which may involve enlargement of the sensory hyperresponsive neural network of the brain until a critical neural mass is reached and initiation of seizures results.

Amygdala↗
PubMed1985

Mechanisms of sensory seizures: brain-stem neuronal response changes and convulsant drugs.

Generalized convulsive seizures can be triggered by sensory stimuli in animals treated with subthreshold levels of convulsant drugs. The sensory responses of the brain-stem reticular formation (RF) are extensively enhanced before seizure initiation with bicuculline, strychnine, pentylenetetrazol, physostigmine, and several other convulsants. The responses of RF neurons are more greatly enhanced than other nonprimary neurons in the hippocampus, amygdala, and cortex. The action of systemically administered convulsants involves direct effects on reticular neurons, because RF response enhancement is also seen with iontophoresis. RF neuronal response enhancement does not appear to involve actions of convulsants on specific neurotransmitters, because agents that act on different transmitters enhance the responses of the same RF neuron when given sequentially. Anticonvulsant drugs reverse the effects of convulsants on reticular neurons. The convulsant-induced response enhancement in the RF may involve blockade of inhibitory postsynaptic potentials and/or threshold reduction, effects observed in vitro. RF neurons may be most susceptible to convulsant action because these agents block habituation and other mechanisms that normally restrict RF neuronal responsiveness. The massive synchronization of reticular neuronal firing by sensory stimuli may induce seizures by intense output over widespread RF projection pathways analogous to the afterdischarge seizures seen with electrical stimulation of the RF.

Animals↗
PubMed1984

Effects of iontophoretic application of convulsants on the sensory responses of neurons in the brain-stem reticular formation.

Iontophoretic or pneumatic application of convulsants produced enhancement of the sensory responses of brain-stem reticular formation (RF) neurons in cat and rat. Enhanced sensory responsiveness is observed with visual, auditory, somatosensory and vibrissa manipulation following application of strychnine, bicuculline or pentylenetetrazol. The effect was not transmitter-specific, since it could be produced by sequential application of bicuculline and strychnine which are thought to affect different neurotransmitters. Intravenous administration of convulsant also enhanced the responsiveness of RF neurons which had previously been affected by application of a different convulsant. Both systemic and iontophoretic effects could be antagonized by application of GABA and glycine. These data, coupled with previous findings in primary sensory pathways, indicate that sensory response enhancement in the RF induced by intravenous administration of these convulsants is in large part due to actions on synaptic elements of reticular formation neurons.

Animals↗
PubMed1984

Baclofen reduces tone-evoked activity of cochlear nucleus neurons.

Recent evidence suggests that an excitant amino acid may be a neurotransmitter at acoustic nerve synapses in cochlear nucleus (CN). Release of excitant amino acids is reportedly reduced by baclofen, a lipophilic GABA-mimetic used to treat the spasticity of multiple sclerosis and spinal injury. Microiontophoresis of (-)baclofen suppressed spontaneous and tone-evoked activity in CN neurons. GABA inhibited the responses of most neurons responsive to (-)baclofen. However, iontophoresis of these two substances onto the same CN neuron resulted in dramatic differences in time course to maximum effect and to recovery. Onset and offset of (-)baclofen-induced firing reduction were gradual at all doses (currents), but even the highest doses rarely caused total suppression of firing. Inhibition of firing by GABA was abrupt, and total suppression was frequently observed over the range of doses used. GABA desensitization (fading) commonly occurred while the (-)baclofen response never faded. The same CN neurons were also suppressed by D-alpha-aminoadipate, which blocks certain excitatory amino acid receptors, while the GABA antagonist bicuculline had no effect on the (-)baclofen response. These findings support the hypothesis that an excitant amino acid may be a transmitter at acoustic nerve synapses in CN.

2-Aminoadipic Acid↗
PubMed1983

Bicuculline-induced enhancement of sensory responses and cross-correlations between reticular formation and cortical neurons.

The visual, auditory and somatosensory responses of neurons in the brain stem reticular formation (RF) and pericruciate cortex of the cat are enhanced by intravenous administration of subconvulsant doses of bicuculline. The degree of enhancement in RF neurons is somewhat greater in magnitude and occurs in a greater percentage of RF neurons. The latency of response is shorter in the RF than in the cortex in 70% of cases. A large percentage of simultaneously recorded RF and cortical neurons which became responsive to the same stimulus exhibited consistent convulsant-induced cross-correlations of firing which were not present before drug treatment. The latency and correlation data are consistent with the possibility that the RF may subserve the cortical enhancement. Auditory response thresholds in RF neurons are reduced by bicuculline administration. Enhancement of RF neuronal responsiveness has previously been observed with several other convulsant drugs which are thought to act on different neurotransmitters suggesting that it may reflect a general action of these agents beyond the effects on specific neurotransmitters. The bicuculline-induced correlation of firing of RF and pericruciate neurons may be involved in the mechanism of initiation of convulsant-mediated seizure generalization induced by sensory stimuli.

Animals↗
PubMed1983

Effects of acetylcholine on cochlear nucleus neurons.

Iontophoretic application of acetylcholine (ACh) onto neurons in the dorsal cochlear nucleus (DCN) resulted in an inhibition of the tone-evoked responses of 85% of neurons which were affected. That effect in the DCN contrasts with the predominance of excitatory effects of ACh seen in ventral cochlear nucleus (VCN) neurons. The ACh-induced inhibition in the DCN had a considerably slower onset and time course of recovery than that seen with glycine-induced inhibition. The degree of ACh effects was constant with increasing intensity or attained a maximum effect at 20 to 30 dB above best-frequency threshold in contrast to glycine, which had effects that were relatively greater at low intensities. These findings suggested a modulatory role for ACh at DCN and VCN synapses.

Acetylcholine↗
PubMed1983

On the site of pentylenetetrazol-induced enhancement of auditory responses of the reticular formation: localized cooling and electrical stimulation studies.

Pentylenetetrazol (PTZ), administered systemically, enhanced the auditory responses of neurons of the mesencephalic reticular formation (MRF). Responses evoked in the mesencephalic reticular formation by electrical stimuli in several primary auditory nuclei (cochlear nucleus, superior olivary complex and lateral lemniscus, but not inferior colliculus) were also enhanced by pentylenetetrazol in the majority of cases. Bilateral cryoprobe cooling in the lateral lemniscal tract substantially reduced the auditory-evoked field potentials (EPs) in the mesencephalic reticular formation before and after administration of pentylenetetrazol. Cooling in the inferior colliculus (IC) produced a small reduction in auditory-evoked field potentials in the mesencephalic reticular formation before drug but a more substantial degree of reduction after administration of pentylenetetrazol. A relatively small degree of pentylenetetrazol-induced enhancement of the response was seen in neurons of the inferior colliculus (158% of control) as compared to that of neurons in the mesencephalic reticular formation (410%). These findings would be consistent with the reported ability of pentylenetetrazol to block presynaptic inhibition if the input from the inferior colliculus to the mesencephalic reticular formation has inhibitory as well as excitatory components. These data along with the present authors' recent finding of enhancement of response with microapplication of convulsants strongly suggest that enhancement of responses of neurons of the mesencephalic reticular formation, induced by systemically administered convulsants such as pentylenetetrazol is exerted, to a large extent, by direct actions on synaptic elements of the reticular formation.

Animals↗
PubMed1983

Strychnine blocks binaural inhibition in lateral superior olivary neurons.

The present study seeks to identify neurotransmitters mediating binaural inhibition in lateral superior olivary nucleus neurons. Neurons in this auditory structure receive inputs from both ears and are thought to code for localization of sound in space. Iontophoretic application of glycine during monaural stimulation was found to mimic the inhibition observed with binaural stimulation. Binaural inhibition was blocked by application of the glycine receptor antagonist, strychnine, as were the effects of iontophoretic application of glycine. The post-strychnine recovery time course for return of synaptically mediated binaural inhibition and recovery of the effects of iontophoretic glycine application were identical. Although the superior olivary complex (SOC) neurons displaying binaural inhibition could in some cases be inhibited by GABA, the binaural inhibition rarely was blocked by iontophoretic application of the GABA receptor antagonist, bicuculline. These findings suggest that glycine may be a neurotransmitter mediating binaural inhibition in certain SOC neurons and that the projection to the lateral superior olivary nucleus from the medial nucleus of the trapezoid body may be glycinergic.

Acoustic Stimulation↗
PubMed1981

Glutamate and aspartate: alteration of thresholds and response patterns of auditory neurons.

Iontophoretic application of the excitant amino acids glutamate and aspartate onto neurons in the chinchilla cochlear nucleus results in a lowering of the threshold of response to auditory stimuli. Neurons that display 'on'-type phasic responses to toneburst stimuli may become tonic, sustained responders with iontophoretic application of glutamate or aspartate. The ability of either glutamate or aspartate to effect changes in thresholds and response patterns of cochlear nucleus neurons is further evidence that one of these amino acids may be the afferent transmitter of the auditory nerve. The effects seen with these excitant amino acids may also provide insight into the underlying synaptic events involved in the generation of a particular response pattern.

Animals↗
PubMed1980

A simple technique for constructing 'piggy-back' multibarrel microelectrodes.

A method is described for the construction of a 6-barrel electrode, enabling intra- or extracellular recording from a protruding barrel and iontophoretic ejection from the remaining 5 barrels. This method enables each laboratory to employ the recording electrode most suitable for its research. The supplied needed for the assembly of the 6-barrel electrodes are readily available and economical. The assembly of this 'piggy-back' electrode requires, with a minimal amount of practice, only 10-15 min.

Animals↗
PubMed1979

Frequency-following responses in primary auditory and reticular formation structures.

The responses of the cat brain to tonal stimuli were recorded from the inferior colliculus, medial geniculate, reticular formation and the far field. The response consisted of an onset component and a frequency-following response (FFR) component in the inferior colliculus (IC) and the far field. In contrast to previous work, the FFR was also observed in the reticular formation. The response in the reticular formation was abolished at lower doses of pentobarbital and at lower relative intensities of masking than that in the IC and far field. The amplitude of the FFR increased and the latency decreased with progressive ventral movement of the electrode through the IC. The onset component of the response in IC was more easily masked than the FFR component, while the FFR component was depressed to a somewhat greater extent by pentobarbital administration. These findings suggest that the different components of the response to tonal stimuli are generated by different mechanisms.

Acoustic Stimulation↗