daniel barth | University of Colorado, Boulder (original) (raw)
Papers by daniel barth
Journal of Neurophysiology, Apr 1, 2006
Public reporting burden for this collection of information is estimated to average 1 hour per res... more Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS.
arXiv (Cornell University), Sep 18, 2015
Introductory points. We have read the comments by D'Ambrosio and colleagues, including their supp... more Introductory points. We have read the comments by D'Ambrosio and colleagues, including their supplemental material; these comments have not changed our interpretation of our data (or theirs) or our conclusions. We stand fully behind our paper, as published. (1) We believe all aspects of our experimental design were completely appropriate for studying epileptogenesis; the experimental techniques for fluid percussion injury (FPI) have been used by us and others to study traumatic brain injury (TBI), and our experimental design has been used in other animal models to reveal genuine bona fide acquired epilepsy; (2) We agree that the data from the FPI-treated and control animals in our study were essentially identical, and by extension, we did not induce post-traumatic epilepsy; this was in fact a very important point of our paper; (3) The criteria for separating different types of epileptic seizures that we used is standard and well-accepted across the clinical and experimental literature. The claims of D'Ambrosio and colleagues refer to their prior attempts to re-define the features of different types of seizures to retroactively fit their data from their FPI experiments into a clinical context; integral to our concerns about their work is how they studied their control animals; and, (4) Although we did not cite some publications by D'Ambrosio and colleagues, we have cited extensive antecedent literature that is directly relevant to our data (and theirs); their experiments with anti-epileptic drugs and cooling are only indirectly relevant, and we believe these experiments also are questionable if not potentially flawed. Although SWDs appear to have been useful as models for the study of absence seizures, the idiosyncrasies of the sensitivity (or not) of EEEs to various AEDs is peripheral to the core issue. Reports that EEEs are pharmacoresistant to traditional AEDs and convenient models for testing possible new AEDs could reflect that EEEs are simply normal oscillations and not models of the complex partial seizures characteristic of PTE. In spite of the criticisms by D'Ambrosio and colleagues, we see no reason to change anything in our paper; our data directly contradict the hypotheses and conclusions of D'Ambrosio and colleagues, which we believe are fundamentally flawed for several reasons, particularly the widespread and consistent occurrence of epileptiform electrographic events (EEEs) in control animals.
Journal of Neurophysiology
Unilateral-onset spike-wave discharges (SWDs) in rats have been used to model complex partial sei... more Unilateral-onset spike-wave discharges (SWDs) in rats have been used to model complex partial seizures in human posttraumatic epilepsy (PTE), compared to bilateral-onset SWDs thought to reflect human absence seizures. Here, we show that both unilateral- and bilateral-onset SWDs following traumatic brain injury are suppressed by the antiabsence drug ethosuximide and are unaffected by the antiseizure drug carbamazepine. We propose that unilateral-onset SWDs are not useful for studying mechanisms of, or treatments for, PTE.
Compared with other areas of the forebrain, the function of insular cortex is poorly understood. ... more Compared with other areas of the forebrain, the function of insular cortex is poorly understood. This study examined the unisensory and multisensory function of the rat insula using high-resolution, whole-hemisphere, epipial evoked potential mapping. We found the posterior insula to contain distinct auditory and somatotopically organized somatosensory fields with an interposed and overlapping region capable of integrating these sensory modalities. Unisensory and multisensory responses were uninfluenced by complete lesioning of primary and secondary auditory and somatosensory cortices, suggesting a high degree of parallel afferent input from the thalamus. In light of the established connections of the posterior insula with the amygdala, we propose that integration of auditory and somatosensory modalities reported here may play a role in auditory fear conditioning.
The Journal of Neuroscience, 2019
Absence epilepsy is a heritable human neurological disorder characterized by brief nonconvulsive ... more Absence epilepsy is a heritable human neurological disorder characterized by brief nonconvulsive seizures with behavioral arrest, moderate-to-severe loss of consciousness (absence), and distinct spike-wave discharges (SWDs) in the EEG and electrocorticogram (ECoG). Genetic models of this disorder have been created by selectively inbreeding rats for absence seizure-like events with similar electrical and behavioral characteristics. However, these events are also common in outbred laboratory rats, raising concerns about whether SWD/immobility accurately reflects absence epilepsy as opposed to "normal" rodent behavior. We hypothesized that, if SWD/ immobility models absence seizures, it would not exist in wild-caught rats due to the pressures of natural selection. To test this hypothesis, we compared chronic video/electrocorticogram recordings from male and female wild-caught (Brown-Norway [BN]) rats to recordings from laboratory outbred BN, outbred Long-Evans, and inbred WAG/Rij rats (i.e., a model of absence epilepsy). Wild-caught BN rats displayed absence-like SWD/immobility events that were highly similar to outbred BN rats in terms of spike-wave morphology, frequency, diurnal rhythmicity, associated immobility, and sensitivity to the anti-absence drug, ethosuximide; however, SWD bursts were less frequent and of shorter duration in wild-caught and outbred BN rats than the outbred Long-Evans and inbred WAG/Rij strains. We conclude that SWD/immobility in rats does not represent absence seizures, although they appear to have many similarities. In wild rats, SWD/immobility appears to represent normal brain activity that does not reduce survival in natural environments, a conclusion that logically extends to outbred laboratory rats and possibly to those that have been inbred to model absence epilepsy.
Journal of Neurophysiology, 2001
The purpose of this study was to clarify the neurogenesis of thalamically evoked gamma frequency ... more The purpose of this study was to clarify the neurogenesis of thalamically evoked gamma frequency (∼40 Hz) oscillations in auditory cortex by comparing simultaneously recorded extracellular and intracellular responses elicited with electrical stimulation of the posterior intralaminar nucleus of the thalamus (PIL). The focus of evoked gamma activity was located between primary and secondary auditory cortex using a 64-channel epipial electrode array, and all subsequent intracellular recordings and single-electrode field potential recordings were made at this location. These data indicate that PIL stimulation evokes gamma oscillations in auditory cortex by tonically depolarizing pyramidal cells in the supra- and infragranular layers. No cells revealed endogenous membrane properties capable of producing activity in the gamma frequency band when depolarized individually with injected current, but all displayed both sub- and supra-threshold responses time-locked to extracellular fast oscil...
Journal of Neurophysiology, 1997
Brett, Barbara and Daniel S. Barth. Subcortical modulation of high-frequency (gamma band) oscilla... more Brett, Barbara and Daniel S. Barth. Subcortical modulation of high-frequency (gamma band) oscillating potentials in auditory cortex. J. Neurophysiol. 78: 573–581, 1997. The purpose of this study was to use depth electrical stimulation and retrograde horseradish peroxidase (HRP) labeling to determine what role certain subcortical nuclei play in the neurogenesis of high-frequency gamma (∼40 Hz) oscillations in rat auditory cortex. Evoked and spontaneous electrocortical oscillations were recorded with the use of a high-spatial-resolution multichannel epipial electrode array while electrical stimulation was delivered to the posterior intralaminar (PIL) region of the ventral acoustic thalamus and to the centrolateral nucleus (CL) and the nucleus basalis (NB), which have been previously implicated in the production of cortical gamma oscillations. PIL stimulation consistently evoked gamma oscillations confined to a location between primary and secondary auditory cortex, corresponding to th...
Journal of Neurophysiology, 2000
Oscillatory activity in excess of several hundred hertz has been observed in somatosensory evoked... more Oscillatory activity in excess of several hundred hertz has been observed in somatosensory evoked potentials (SEP) recorded in both humans and animals and is attracting increasing interest regarding its role in brain function. Currently, however, little is known about the cellular events underlying these oscillations. The present study employed simultaneous in-vivo intracellular and epipial field-potential recording to investigate the cellular correlates of fast oscillations in rat somatosensory cortex evoked by vibrissa stimulation. Two distinct types of fast oscillations were observed, here termed “fast oscillations” (FO) (200–400 Hz) and “very fast oscillations” (VFO) (400–600 Hz). FO coincided with the earliest slow-wave components of the SEP whereas VFO typically were later and of smaller amplitude. Regular spiking (RS) cells exhibited vibrissa-evoked responses associated with one or both types of fast oscillations and consisted of combinations of spike and/or subthreshold even...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 14, 2017
Genetically inherited absence epilepsy in humans is typically characterized by brief (seconds) sp... more Genetically inherited absence epilepsy in humans is typically characterized by brief (seconds) spontaneous seizures, which involve spike-wave discharges (SWDs) in the EEG and interruption of consciousness and ongoing behavior. Genetic (inbred) models of this disorder in rats have been used to examine mechanisms, comorbidities, and antiabsence drugs. SWDs have also been proposed as models of complex partial seizures (CPSs) following traumatic brain injury (post-traumatic epilepsy). However, the ictal characteristics of these rat models, including SWDs and associated immobility, are also prevalent in healthy outbred laboratory rats. We therefore hypothesized that SWDs are not always associated with classically defined absence seizures or CPSs. To test this hypothesis, we used operant conditioning in male rats to determine whether outbred strains, Sprague Dawley and Long-Evans, and/or the inbred WAG/Rij strain (a rat model of heritable human absence epilepsy) could exercise voluntary c...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 2, 2015
Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors lea... more Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient.We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5.Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent conv...
Neuroscience, 2014
CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance,... more CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance, reward, and dependence/withdrawal. Such effects are mediated by opioid signaling at TLR4, presumptively of glial origin. Whether CNS endothelial cells express TLR4 is controversial. If so, they would be well positioned for activation by blood-borne opioids, contributing to opioidinduced pro-inflammatory responses. These studies examined adult primary rat CNS endothelial cell responses to (-)-morphine or its mu-opioid receptor (MOR) inactive metabolite morphine-3glucuronide (M3G), both known TLR4 agonists. We demonstrate that adult rat CNS endothelial cells express functional TLR4. M3G activated NFκB, increased tumor necrosis factor-α (TNFα) and cyclooxygenase-2 (COX2) mRNAs, and released prostaglandin E 2 from these cells. (-)-Morphine-induced upregulation of TNFα mRNA and prostaglandin E 2 release were unmasked by pre-treatment with nalmefene, a MOR antagonist without TLR4 activity (unlike CTAP, shown to
Brain, 2009
Brain glial cells, five times more prevalent than neurons, have recently received attention for t... more Brain glial cells, five times more prevalent than neurons, have recently received attention for their potential involvement in epileptic seizures. Microglia and astrocytes, associated with inflammatory innate immune responses, are responsible for surveillance of brain damage that frequently results in seizures. Thus, an intriguing suggestion has been put forward that seizures may be facilitated and perhaps triggered by brain immune responses. Indeed, recent evidence strongly implicates innate immune responses in lowering seizure threshold in experimental models of epilepsy, yet, there is no proof that they can play an independent role in initiating seizures in vivo. Here, we show that cortical innate immune responses alone produce profound increases of brain excitability resulting in focal seizures. We found that cortical application of lipopolysaccharide, binding to toll-like receptor 4 (TLR4), triples evoked field potential amplitudes and produces focal epileptiform discharges. These effects are prevented by pre-application of interleukin-1 receptor antagonist. Our results demonstrate how the innate immune response may participate in acute seizures, increasing neuronal excitability through interleukin-1 release in response to TLR4 detection of the danger signals associated with infections of the central nervous system and with brain injury. These results suggest an important role of innate immunity in epileptogenesis and focus on glial inhibition, through pharmacological blockade of TLR4 and the pro-inflammatory mediators released by activated glia, in the study and treatment of seizure disorders in humans.
The Journal of Neuroscience, 2008
Safety signals are learned cues that predict stress-free periods whereas behavioral control is th... more Safety signals are learned cues that predict stress-free periods whereas behavioral control is the ability to modify a stressor by behavioral actions. Both serve to attenuate the effects of stressors such as uncontrollable shocks. Internal and external cues produced by a controlling behavior are followed by a stressor-free interval, and so it is possible that safety learning is fundamental to the effect of control. If this is the case then behavioral control and safety should recruit the same neural machinery. Interestingly, safety signals that prevented a behavioral outcome of stressor exposure that is also blocked by control (reduced social exploration) failed to inhibit activity in the dorsal raphé nucleus or use the ventromedial prefrontal cortex, the mechanisms by which behavioral control operates. However, bilateral lesions to a region of posterior insular cortex, termed the “sensory insula,” prevented the effect of safety but not of behavioral control, providing a double-diss...
Journal of Neurophysiology, 2004
In rodents, as in other species, regions of secondary somatosensory cortex (SII) may be distingui... more In rodents, as in other species, regions of secondary somatosensory cortex (SII) may be distinguished from primary cortex (SI) both anatomically and electrophysiologically. However, the number of rodent SII subregions, their somatotopic organization, and their function are poorly understood. The presence of multisensory responsive neurons in some areas of SII suggests that one of its roles may be in the integration of somatosensory information with information from other sensory modalities. In this study, we used auditory, somatosensory, or combined auditory/somatosensory stimuli, and high-resolution epipial-evoked potential maps of rat SII to identify the number of spatially discrete subregions, estimate their somatotopic organization, and delineate regions with multisensory response properties. Maps revealed two distinct subregions within SII, one rostral and the other caudal, which were situated lateral to the posteromedial barrel subfield. Distinct somatotopies were evident at b...
Journal of Neurophysiology, 1998
Sukov, William and Daniel S. Barth. Three-dimensional analysis of spontaneous and thalamically ev... more Sukov, William and Daniel S. Barth. Three-dimensional analysis of spontaneous and thalamically evoked gamma oscillations in auditory cortex. J. Neurophysiol. 79: 2875–2884, 1998. The purpose of this study was to investigate interactions among laminar cell populations producing spontaneous and evoked high-frequency (∼40 Hz) gamma oscillations in auditory cortex. Electrocortical oscillations were recorded using a 64-channel epipial electrode array and a 16-channel linear laminar electrode array while electrical stimulation was delivered to the posterior intralaminar (PIL) nucleus. Spontaneous gamma oscillations, and those evoked by PIL stimulation, are confined to a location overlapping primary and secondary auditory cortex. Current source-density and principal components analysis of laminar recordings at this site indicate that the auditory evoked potential (AEP) complex is characterized by a stereotyped asynchronous activation of supra- and infragranular cell populations. Similar an...
Journal of Neurophysiology, 1999
A 64-channel electrode array was used to study the spatial and temporal characteristics of fast (... more A 64-channel electrode array was used to study the spatial and temporal characteristics of fast (>200 Hz) electrical oscillations recorded from the surface of rat cortex in both awake and anesthetized animals. Transient vibrissal displacements were effective in evoking oscillatory responses in the vibrissa/barrel field and were tightly time-locked to stimulus onset, coinciding with the earliest temporal components of the coincident slow-wave response. Vibrissa-evoked fast oscillations exhibited modality specificity and were earliest and of largest amplitude over the cortical barrel, which corresponded to the vibrissa stimulated, spreading to sequentially engage neighboring barrels over subsequent oscillatory cycles. The response was enhanced after paired-vibrissal stimulation and was sensitive to time delays between movement of separate vibrissae. These data suggest that spatiotemporal interactions between fast oscillatory bursts in the barrel field may play a role in rapidly int...
Journal of Neurophysiology, 1998
MacDonald, Kurt D., Eva Fifkova, Michael S. Jones, and Daniel S. Barth. Focal stimulation of the ... more MacDonald, Kurt D., Eva Fifkova, Michael S. Jones, and Daniel S. Barth. Focal stimulation of the thalamic reticular nucleus induces focal gamma waves in cortex. J. Neurophysiol. 79: 474–477, 1998. Electrical stimulation of the thalamic reticular nucleus (TRN; 0.5-s trains of 500-Hz 0.5-ms pulses at 5–10 μA) evokes focal oscillations of cortical electrical potentials in the gamma frequency band (∼35–55 Hz). These evoked oscillations are specific to either the somatosensory or auditory cortex and to subregions of the cortical receptotopic map, depending on what part of the TRN is stimulated. Focal stimulation of the internal capsule, however, evokes focal slow potentials, without gamma activity. Our results suggest that the TRN's role extends beyond that of general cortical arousal to include specific modality and submodality activation of the forebrain.
Journal of Neurophysiology
Although convulsive seizures occurring during pilocarpine-induced epileptogenesis have received c... more Although convulsive seizures occurring during pilocarpine-induced epileptogenesis have received considerable attention, nonconvulsive seizures have not been closely examined, even though they may reflect the earliest signs of epileptogenesis and potentially guide research on antiepileptogenic interventions. The definition of nonconvulsive seizures based on brain electrical activity alone has been controversial. Here we define and quantify electrographic properties of convulsive and nonconvulsive seizures in the context of the acquired epileptogenesis that occurs after pilocarpine-induced status epilepticus (SE). Lithium-pilocarpine was used to induce the prolonged repetitive seizures characteristic of SE; when SE was terminated with paraldehyde, seizures returned during the 2-day period after pilocarpine treatment. A distinct latent period ranging from several days to >2 wk was then measured with continuous, long-term video-EEG. Nonconvulsive seizures dominated the onset of epile...
Journal of Neurophysiology, Apr 1, 2006
Public reporting burden for this collection of information is estimated to average 1 hour per res... more Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS.
arXiv (Cornell University), Sep 18, 2015
Introductory points. We have read the comments by D'Ambrosio and colleagues, including their supp... more Introductory points. We have read the comments by D'Ambrosio and colleagues, including their supplemental material; these comments have not changed our interpretation of our data (or theirs) or our conclusions. We stand fully behind our paper, as published. (1) We believe all aspects of our experimental design were completely appropriate for studying epileptogenesis; the experimental techniques for fluid percussion injury (FPI) have been used by us and others to study traumatic brain injury (TBI), and our experimental design has been used in other animal models to reveal genuine bona fide acquired epilepsy; (2) We agree that the data from the FPI-treated and control animals in our study were essentially identical, and by extension, we did not induce post-traumatic epilepsy; this was in fact a very important point of our paper; (3) The criteria for separating different types of epileptic seizures that we used is standard and well-accepted across the clinical and experimental literature. The claims of D'Ambrosio and colleagues refer to their prior attempts to re-define the features of different types of seizures to retroactively fit their data from their FPI experiments into a clinical context; integral to our concerns about their work is how they studied their control animals; and, (4) Although we did not cite some publications by D'Ambrosio and colleagues, we have cited extensive antecedent literature that is directly relevant to our data (and theirs); their experiments with anti-epileptic drugs and cooling are only indirectly relevant, and we believe these experiments also are questionable if not potentially flawed. Although SWDs appear to have been useful as models for the study of absence seizures, the idiosyncrasies of the sensitivity (or not) of EEEs to various AEDs is peripheral to the core issue. Reports that EEEs are pharmacoresistant to traditional AEDs and convenient models for testing possible new AEDs could reflect that EEEs are simply normal oscillations and not models of the complex partial seizures characteristic of PTE. In spite of the criticisms by D'Ambrosio and colleagues, we see no reason to change anything in our paper; our data directly contradict the hypotheses and conclusions of D'Ambrosio and colleagues, which we believe are fundamentally flawed for several reasons, particularly the widespread and consistent occurrence of epileptiform electrographic events (EEEs) in control animals.
Journal of Neurophysiology
Unilateral-onset spike-wave discharges (SWDs) in rats have been used to model complex partial sei... more Unilateral-onset spike-wave discharges (SWDs) in rats have been used to model complex partial seizures in human posttraumatic epilepsy (PTE), compared to bilateral-onset SWDs thought to reflect human absence seizures. Here, we show that both unilateral- and bilateral-onset SWDs following traumatic brain injury are suppressed by the antiabsence drug ethosuximide and are unaffected by the antiseizure drug carbamazepine. We propose that unilateral-onset SWDs are not useful for studying mechanisms of, or treatments for, PTE.
Compared with other areas of the forebrain, the function of insular cortex is poorly understood. ... more Compared with other areas of the forebrain, the function of insular cortex is poorly understood. This study examined the unisensory and multisensory function of the rat insula using high-resolution, whole-hemisphere, epipial evoked potential mapping. We found the posterior insula to contain distinct auditory and somatotopically organized somatosensory fields with an interposed and overlapping region capable of integrating these sensory modalities. Unisensory and multisensory responses were uninfluenced by complete lesioning of primary and secondary auditory and somatosensory cortices, suggesting a high degree of parallel afferent input from the thalamus. In light of the established connections of the posterior insula with the amygdala, we propose that integration of auditory and somatosensory modalities reported here may play a role in auditory fear conditioning.
The Journal of Neuroscience, 2019
Absence epilepsy is a heritable human neurological disorder characterized by brief nonconvulsive ... more Absence epilepsy is a heritable human neurological disorder characterized by brief nonconvulsive seizures with behavioral arrest, moderate-to-severe loss of consciousness (absence), and distinct spike-wave discharges (SWDs) in the EEG and electrocorticogram (ECoG). Genetic models of this disorder have been created by selectively inbreeding rats for absence seizure-like events with similar electrical and behavioral characteristics. However, these events are also common in outbred laboratory rats, raising concerns about whether SWD/immobility accurately reflects absence epilepsy as opposed to "normal" rodent behavior. We hypothesized that, if SWD/ immobility models absence seizures, it would not exist in wild-caught rats due to the pressures of natural selection. To test this hypothesis, we compared chronic video/electrocorticogram recordings from male and female wild-caught (Brown-Norway [BN]) rats to recordings from laboratory outbred BN, outbred Long-Evans, and inbred WAG/Rij rats (i.e., a model of absence epilepsy). Wild-caught BN rats displayed absence-like SWD/immobility events that were highly similar to outbred BN rats in terms of spike-wave morphology, frequency, diurnal rhythmicity, associated immobility, and sensitivity to the anti-absence drug, ethosuximide; however, SWD bursts were less frequent and of shorter duration in wild-caught and outbred BN rats than the outbred Long-Evans and inbred WAG/Rij strains. We conclude that SWD/immobility in rats does not represent absence seizures, although they appear to have many similarities. In wild rats, SWD/immobility appears to represent normal brain activity that does not reduce survival in natural environments, a conclusion that logically extends to outbred laboratory rats and possibly to those that have been inbred to model absence epilepsy.
Journal of Neurophysiology, 2001
The purpose of this study was to clarify the neurogenesis of thalamically evoked gamma frequency ... more The purpose of this study was to clarify the neurogenesis of thalamically evoked gamma frequency (∼40 Hz) oscillations in auditory cortex by comparing simultaneously recorded extracellular and intracellular responses elicited with electrical stimulation of the posterior intralaminar nucleus of the thalamus (PIL). The focus of evoked gamma activity was located between primary and secondary auditory cortex using a 64-channel epipial electrode array, and all subsequent intracellular recordings and single-electrode field potential recordings were made at this location. These data indicate that PIL stimulation evokes gamma oscillations in auditory cortex by tonically depolarizing pyramidal cells in the supra- and infragranular layers. No cells revealed endogenous membrane properties capable of producing activity in the gamma frequency band when depolarized individually with injected current, but all displayed both sub- and supra-threshold responses time-locked to extracellular fast oscil...
Journal of Neurophysiology, 1997
Brett, Barbara and Daniel S. Barth. Subcortical modulation of high-frequency (gamma band) oscilla... more Brett, Barbara and Daniel S. Barth. Subcortical modulation of high-frequency (gamma band) oscillating potentials in auditory cortex. J. Neurophysiol. 78: 573–581, 1997. The purpose of this study was to use depth electrical stimulation and retrograde horseradish peroxidase (HRP) labeling to determine what role certain subcortical nuclei play in the neurogenesis of high-frequency gamma (∼40 Hz) oscillations in rat auditory cortex. Evoked and spontaneous electrocortical oscillations were recorded with the use of a high-spatial-resolution multichannel epipial electrode array while electrical stimulation was delivered to the posterior intralaminar (PIL) region of the ventral acoustic thalamus and to the centrolateral nucleus (CL) and the nucleus basalis (NB), which have been previously implicated in the production of cortical gamma oscillations. PIL stimulation consistently evoked gamma oscillations confined to a location between primary and secondary auditory cortex, corresponding to th...
Journal of Neurophysiology, 2000
Oscillatory activity in excess of several hundred hertz has been observed in somatosensory evoked... more Oscillatory activity in excess of several hundred hertz has been observed in somatosensory evoked potentials (SEP) recorded in both humans and animals and is attracting increasing interest regarding its role in brain function. Currently, however, little is known about the cellular events underlying these oscillations. The present study employed simultaneous in-vivo intracellular and epipial field-potential recording to investigate the cellular correlates of fast oscillations in rat somatosensory cortex evoked by vibrissa stimulation. Two distinct types of fast oscillations were observed, here termed “fast oscillations” (FO) (200–400 Hz) and “very fast oscillations” (VFO) (400–600 Hz). FO coincided with the earliest slow-wave components of the SEP whereas VFO typically were later and of smaller amplitude. Regular spiking (RS) cells exhibited vibrissa-evoked responses associated with one or both types of fast oscillations and consisted of combinations of spike and/or subthreshold even...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 14, 2017
Genetically inherited absence epilepsy in humans is typically characterized by brief (seconds) sp... more Genetically inherited absence epilepsy in humans is typically characterized by brief (seconds) spontaneous seizures, which involve spike-wave discharges (SWDs) in the EEG and interruption of consciousness and ongoing behavior. Genetic (inbred) models of this disorder in rats have been used to examine mechanisms, comorbidities, and antiabsence drugs. SWDs have also been proposed as models of complex partial seizures (CPSs) following traumatic brain injury (post-traumatic epilepsy). However, the ictal characteristics of these rat models, including SWDs and associated immobility, are also prevalent in healthy outbred laboratory rats. We therefore hypothesized that SWDs are not always associated with classically defined absence seizures or CPSs. To test this hypothesis, we used operant conditioning in male rats to determine whether outbred strains, Sprague Dawley and Long-Evans, and/or the inbred WAG/Rij strain (a rat model of heritable human absence epilepsy) could exercise voluntary c...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 2, 2015
Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors lea... more Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient.We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5.Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent conv...
Neuroscience, 2014
CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance,... more CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance, reward, and dependence/withdrawal. Such effects are mediated by opioid signaling at TLR4, presumptively of glial origin. Whether CNS endothelial cells express TLR4 is controversial. If so, they would be well positioned for activation by blood-borne opioids, contributing to opioidinduced pro-inflammatory responses. These studies examined adult primary rat CNS endothelial cell responses to (-)-morphine or its mu-opioid receptor (MOR) inactive metabolite morphine-3glucuronide (M3G), both known TLR4 agonists. We demonstrate that adult rat CNS endothelial cells express functional TLR4. M3G activated NFκB, increased tumor necrosis factor-α (TNFα) and cyclooxygenase-2 (COX2) mRNAs, and released prostaglandin E 2 from these cells. (-)-Morphine-induced upregulation of TNFα mRNA and prostaglandin E 2 release were unmasked by pre-treatment with nalmefene, a MOR antagonist without TLR4 activity (unlike CTAP, shown to
Brain, 2009
Brain glial cells, five times more prevalent than neurons, have recently received attention for t... more Brain glial cells, five times more prevalent than neurons, have recently received attention for their potential involvement in epileptic seizures. Microglia and astrocytes, associated with inflammatory innate immune responses, are responsible for surveillance of brain damage that frequently results in seizures. Thus, an intriguing suggestion has been put forward that seizures may be facilitated and perhaps triggered by brain immune responses. Indeed, recent evidence strongly implicates innate immune responses in lowering seizure threshold in experimental models of epilepsy, yet, there is no proof that they can play an independent role in initiating seizures in vivo. Here, we show that cortical innate immune responses alone produce profound increases of brain excitability resulting in focal seizures. We found that cortical application of lipopolysaccharide, binding to toll-like receptor 4 (TLR4), triples evoked field potential amplitudes and produces focal epileptiform discharges. These effects are prevented by pre-application of interleukin-1 receptor antagonist. Our results demonstrate how the innate immune response may participate in acute seizures, increasing neuronal excitability through interleukin-1 release in response to TLR4 detection of the danger signals associated with infections of the central nervous system and with brain injury. These results suggest an important role of innate immunity in epileptogenesis and focus on glial inhibition, through pharmacological blockade of TLR4 and the pro-inflammatory mediators released by activated glia, in the study and treatment of seizure disorders in humans.
The Journal of Neuroscience, 2008
Safety signals are learned cues that predict stress-free periods whereas behavioral control is th... more Safety signals are learned cues that predict stress-free periods whereas behavioral control is the ability to modify a stressor by behavioral actions. Both serve to attenuate the effects of stressors such as uncontrollable shocks. Internal and external cues produced by a controlling behavior are followed by a stressor-free interval, and so it is possible that safety learning is fundamental to the effect of control. If this is the case then behavioral control and safety should recruit the same neural machinery. Interestingly, safety signals that prevented a behavioral outcome of stressor exposure that is also blocked by control (reduced social exploration) failed to inhibit activity in the dorsal raphé nucleus or use the ventromedial prefrontal cortex, the mechanisms by which behavioral control operates. However, bilateral lesions to a region of posterior insular cortex, termed the “sensory insula,” prevented the effect of safety but not of behavioral control, providing a double-diss...
Journal of Neurophysiology, 2004
In rodents, as in other species, regions of secondary somatosensory cortex (SII) may be distingui... more In rodents, as in other species, regions of secondary somatosensory cortex (SII) may be distinguished from primary cortex (SI) both anatomically and electrophysiologically. However, the number of rodent SII subregions, their somatotopic organization, and their function are poorly understood. The presence of multisensory responsive neurons in some areas of SII suggests that one of its roles may be in the integration of somatosensory information with information from other sensory modalities. In this study, we used auditory, somatosensory, or combined auditory/somatosensory stimuli, and high-resolution epipial-evoked potential maps of rat SII to identify the number of spatially discrete subregions, estimate their somatotopic organization, and delineate regions with multisensory response properties. Maps revealed two distinct subregions within SII, one rostral and the other caudal, which were situated lateral to the posteromedial barrel subfield. Distinct somatotopies were evident at b...
Journal of Neurophysiology, 1998
Sukov, William and Daniel S. Barth. Three-dimensional analysis of spontaneous and thalamically ev... more Sukov, William and Daniel S. Barth. Three-dimensional analysis of spontaneous and thalamically evoked gamma oscillations in auditory cortex. J. Neurophysiol. 79: 2875–2884, 1998. The purpose of this study was to investigate interactions among laminar cell populations producing spontaneous and evoked high-frequency (∼40 Hz) gamma oscillations in auditory cortex. Electrocortical oscillations were recorded using a 64-channel epipial electrode array and a 16-channel linear laminar electrode array while electrical stimulation was delivered to the posterior intralaminar (PIL) nucleus. Spontaneous gamma oscillations, and those evoked by PIL stimulation, are confined to a location overlapping primary and secondary auditory cortex. Current source-density and principal components analysis of laminar recordings at this site indicate that the auditory evoked potential (AEP) complex is characterized by a stereotyped asynchronous activation of supra- and infragranular cell populations. Similar an...
Journal of Neurophysiology, 1999
A 64-channel electrode array was used to study the spatial and temporal characteristics of fast (... more A 64-channel electrode array was used to study the spatial and temporal characteristics of fast (>200 Hz) electrical oscillations recorded from the surface of rat cortex in both awake and anesthetized animals. Transient vibrissal displacements were effective in evoking oscillatory responses in the vibrissa/barrel field and were tightly time-locked to stimulus onset, coinciding with the earliest temporal components of the coincident slow-wave response. Vibrissa-evoked fast oscillations exhibited modality specificity and were earliest and of largest amplitude over the cortical barrel, which corresponded to the vibrissa stimulated, spreading to sequentially engage neighboring barrels over subsequent oscillatory cycles. The response was enhanced after paired-vibrissal stimulation and was sensitive to time delays between movement of separate vibrissae. These data suggest that spatiotemporal interactions between fast oscillatory bursts in the barrel field may play a role in rapidly int...
Journal of Neurophysiology, 1998
MacDonald, Kurt D., Eva Fifkova, Michael S. Jones, and Daniel S. Barth. Focal stimulation of the ... more MacDonald, Kurt D., Eva Fifkova, Michael S. Jones, and Daniel S. Barth. Focal stimulation of the thalamic reticular nucleus induces focal gamma waves in cortex. J. Neurophysiol. 79: 474–477, 1998. Electrical stimulation of the thalamic reticular nucleus (TRN; 0.5-s trains of 500-Hz 0.5-ms pulses at 5–10 μA) evokes focal oscillations of cortical electrical potentials in the gamma frequency band (∼35–55 Hz). These evoked oscillations are specific to either the somatosensory or auditory cortex and to subregions of the cortical receptotopic map, depending on what part of the TRN is stimulated. Focal stimulation of the internal capsule, however, evokes focal slow potentials, without gamma activity. Our results suggest that the TRN's role extends beyond that of general cortical arousal to include specific modality and submodality activation of the forebrain.
Journal of Neurophysiology
Although convulsive seizures occurring during pilocarpine-induced epileptogenesis have received c... more Although convulsive seizures occurring during pilocarpine-induced epileptogenesis have received considerable attention, nonconvulsive seizures have not been closely examined, even though they may reflect the earliest signs of epileptogenesis and potentially guide research on antiepileptogenic interventions. The definition of nonconvulsive seizures based on brain electrical activity alone has been controversial. Here we define and quantify electrographic properties of convulsive and nonconvulsive seizures in the context of the acquired epileptogenesis that occurs after pilocarpine-induced status epilepticus (SE). Lithium-pilocarpine was used to induce the prolonged repetitive seizures characteristic of SE; when SE was terminated with paraldehyde, seizures returned during the 2-day period after pilocarpine treatment. A distinct latent period ranging from several days to >2 wk was then measured with continuous, long-term video-EEG. Nonconvulsive seizures dominated the onset of epile...