G Teskey | University of Calgary (original) (raw)

Papers by G Teskey

of Development and testing of a new system for assessing wheel-running behaviour in rodents

Additional file 1: Figure S1. A schematic overview of the system used for assessing wheel-running... more Additional file 1: Figure S1. A schematic overview of the system used for assessing wheel-running behaviour in rodents. A: A picture of the running wheel, angular encoder, and dimensions. B: A schematic overview of the system using LabVIEW system design software (National Instruments). A laptop computer (IBM ThinkPad) with a National Instruments A/D board (NI DAC-Card 6024E, 200 kSamples/s, 16 channels), a breakout box (National Instruments BNC), and a high speed IEEE 1394a port was used to run in-house software to collect raw position data.

Neuron

Farrell et al. resolve the molecular identity and spatiotemporal dynamics of hippocampal endocann... more Farrell et al. resolve the molecular identity and spatiotemporal dynamics of hippocampal endocannabinoid signaling in vivo using a genetically encoded sensor. Compared to physiological activity, seizures result in excessive 2-AG levels, providing substrate for a prolonged stroke-like event.

Neurology

ObjectiveSince the strongest risk factor for sudden unexpected death in epilepsy (SUDEP) is frequ... more ObjectiveSince the strongest risk factor for sudden unexpected death in epilepsy (SUDEP) is frequent bilateral tonic-clonic seizures (BTCS), our aim was to determine whether postictal hypoperfusion in brainstem respiratory centers (BRCs) is more common following tonic-clonic seizures.MethodsWe studied 21 patients with focal epilepsies who underwent perfusion imaging with arterial spin labeling MRI. Subtraction maps of cerebral blood flow were obtained from the postictal and baseline scans. We identified 6 regions of interest in the brainstem that contain key BRCs. Patients were considered to have postictal BRC hypoperfusion if any of the 6 regions of interest were significantly hypoperfused.ResultsAll 6 patients who experienced BTCS during the study had significant clusters of postictal hypoperfusion in BRCs compared to 7 who had focal impaired awareness seizures (7/15). The association between seizure type studied and the presence of BRC hypoperfusion was significant. Duration of e...

eLife, 2016

Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase... more Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neuro...

The Journal of physiology, Jan 29, 2016

The mechanisms by which distinct movements of a forelimb are generated from the same area of moto... more The mechanisms by which distinct movements of a forelimb are generated from the same area of motor cortex have remained elusive. Here we examined a role for HCN channels, given their ability to alter synaptic integration, in the expression of forelimb movement responses during intracortical microstimulation (ICMS) and movements of the forelimb on a skilled reaching task. We used short-duration high resolution ICMS to evoke forelimb movements following pharmacological (ZD7288), experimental (electrically induced cortical seizures) or genetic approaches that we confirmed with whole-cell patch clamp to substantially reduce Ih current. We observed significant increases in the number of multiple movement responses evoked at single sites in motor maps to all 3 experimental manipulations in rats or mice. HCN1(KO) mice were less successful and exhibited atypical movements on a skilled-motor learning task relative to wild-type controls. Furthermore, in reaching-proficient rats, reaching accu...

BMC research notes, Jan 5, 2016

Wheel running is one of the most widely studied behaviours in laboratory rodents. As a result, im... more Wheel running is one of the most widely studied behaviours in laboratory rodents. As a result, improved approaches for the objective monitoring and gathering of more detailed information is increasingly becoming important for evaluating rodent wheel-running behaviour. Here our aim was to develop a new quantitative wheel-running system that can be used for most typical wheel-running experimental protocols. Here we devise a system that can provide a continuous waveform amenable to real-time integration with a high-speed video ideal for wheel-running experimental protocols. While quantification of wheel running behaviour has typically focused on the number of revolutions per unit time as an end point measure, the approach described here allows for more detailed information like wheel rotation fluidity, directionality, instantaneous velocity, and acceleration, in addition to total number of rotations, and the temporal pattern of wheel-running behaviour to be derived from a single trace....

Nature neuroscience, 2016

Overactivation of neuronal N-methyl-D-aspartate receptors (NMDARs) causes excitotoxicity and is n... more Overactivation of neuronal N-methyl-D-aspartate receptors (NMDARs) causes excitotoxicity and is necessary for neuronal death. In the classical view, these ligand-gated Ca(2+)-permeable ionotropic receptors require co-agonists and membrane depolarization for activation. We report that NMDARs signal during ligand binding without activation of their ion conduction pore. Pharmacological pore block with MK-801, physiological pore block with Mg(2+) or a Ca(2+)-impermeable NMDAR variant prevented NMDAR currents, but did not block excitotoxic dendritic blebbing and secondary currents induced by exogenous NMDA. NMDARs, Src kinase and Panx1 form a signaling complex, and activation of Panx1 required phosphorylation at Y308. Disruption of this NMDAR-Src-Panx1 signaling complex in vitro or in vivo by administration of an interfering peptide either before or 2 h after ischemia or stroke was neuroprotective. Our observations provide insights into a new signaling modality of NMDARs that has broad-r...

Journal of Neuroscience, 2014

Alterations in synaptic endocannabinoid signaling are a widespread neurobiological consequence of... more Alterations in synaptic endocannabinoid signaling are a widespread neurobiological consequence of many in vivo experiences, including stress. Here, we report that stressor salience is critical for bidirectionally modifying presynaptic CB-1 receptor (CB1R) function at hypothalamic GABA synapses controlling the neuroendocrine stress axis in male rats. While repetitive, predictable stressor exposure impairs presynaptic CB1R function, these changes are rapidly reversed upon exposure to a high salience experience such as novel stress or by manipulations that enhance neural activity levels in vivo or in vitro. Together these data demonstrate that experience salience, through alterations in afferent synaptic activity, induces rapid changes in endocannabinoid signaling.

International Encyclopedia of the Social & Behavioral Sciences, 2015

The Paradoxical Brain, 2009

Journal of Neuroscience, 2008

Synapse, 2004

Long-term potentiation (LTP) and long-term depression (LTD) are currently the most widely investi... more Long-term potentiation (LTP) and long-term depression (LTD) are currently the most widely investigated models of the synaptic mechanisms underlying learning and memory. Previous research has shown that induction of LTP increases measures of pyramidal cell dendritic morphology in the hippocampus and layers III and V of the neocortex. However, to date there are no reports on the direct effects of LTD induction on dendritic morphology. Here, we investigated the effects of LTD induction on sensorimotor pyramidal cell dendritic morphology. Rats carried a stimulating electrode in the corpus callosum (midline) and a recording electrode in the right sensorimotor cortex. Each rat received low-frequency stimulation composed of 900 pulses at 1 Hz or handling daily for a total 15 days. Evoked potentials (EPs) of the transcallosal pathway were recorded in the right hemisphere before and after the 15 days of stimulation or handling. The rats were then perfused with saline and the brains were immediately processed for Golgi-Cox staining. Our results show that LTD induction is related to decreases in dendritic length and spine density both in layers III and V as well as a decrease in dendritic branch complexity in layer V of the sensorimotor cortex. Thus, neuronal alterations following modifications in neocortical synaptic efficacy may provide a general mechanism for the physical instantiation of learning and memory. Synapse 53:114-121, 2004.

Synapse, 2006

Previous research has shown that seizures kindled in the corpus callosum result in a persistent e... more Previous research has shown that seizures kindled in the corpus callosum result in a persistent enhancement of the callosal-neocortical evoked response but only a transient reduction in layer III pyramidal cell morphology. To date, there are no reports on the direct effects of repeated seizures on dendritic morphology in layer V, the pyramidal layer thought to mediate the kindling-induced enhanced evoked response. This experiment examined the effect of repeated seizures elicited from the corpus callosum, at the level of the frontal neocortex, on the morphology of sensorimotor frontal (Fr1) and occipital (OC1) neocortical layer V, as well as striatal and neuronal dendrites, in male rats. After 25 days of electrically elicited seizures or handling control, rats were sacrificed either 2 days or 3 weeks following the last seizure and processed for Golgi-Cox staining. Analysis of the impregnated pyramidal cell dendrites indicated a significant increase in the amount of dendritic length and branching in rats 2 days, but a decrease 3 weeks, following the last seizure. There was no effect at the distant occipital site. The differential effect between layer V pyramidal neurons and layer III pyramidal neurons suggests that these areas play different roles in the expression of seizures and the adaptation of the brain to the persistent effect of kindling.

Science, 1983

The terrestrial snail Cepaea nemoralis, when placed on a 40 degrees C hot plate, lifts the anteri... more The terrestrial snail Cepaea nemoralis, when placed on a 40 degrees C hot plate, lifts the anterior portion of its foot. The latency of this response is influenced by morphine and by naloxone in a dose-dependent and time-dependent manner. Morphine increases the time taken to respond, whereas naloxone reduces it. Furthermore, naloxone abolishes the effect of morphine. These results indicate that an opiate system may have a role in this behavior, which resembles that reported in vertebrates.

Physiology & Behavior, 1984

KAVALIERS, M., M. HIRST AND G. C. TESKEY. Opioid-induced feeding in the slug, Limax maximus. PHYS... more KAVALIERS, M., M. HIRST AND G. C. TESKEY. Opioid-induced feeding in the slug, Limax maximus. PHYSIOL BEHAV 33(5) 765-767, 1984.-Administration of the opioid agonist, morphine (I and 10 mg kg-1), resulted in significant, dose-dependent increases in the ingestive responses of food-deprived slugs, Limax maximus, and in the initiation of feeding in satiated animals. These effects could be blocked by the opiate antagonist, naioxone (1 mg kg-l), with naloxone by itself causing a significant decrease in the feeding of food-deprived slugs. These results suggest that opiates are involved in the

Pharmacology Biochemistry and Behavior, 1986

Admmlstratmn of the prototyplcal mu opmte agomst, morphine sulphate, 1-10 mg/kg, produced over th... more Admmlstratmn of the prototyplcal mu opmte agomst, morphine sulphate, 1-10 mg/kg, produced over three hours a stgmficant dose-dependent increase m the ingestive responses of free-feeding slugs, Lirnax max~mus, although lower doses,

Pharmacology Biochemistry and Behavior, 1987

Automated multl)artate measurement of spontaneous motor a~ ttrtt~ m ml~ e Ttme ~ ourse and rehabt... more Automated multl)artate measurement of spontaneous motor a~ ttrtt~ m ml~ e Ttme ~ ourse and rehabthttes of the behavu)ral measures PHARMACOLBIOCHEMBEHAV27(3) 565-568 1987-A variety of automated procedures have been developed to measure certain aspects of spontaneous motor activity m small ammals The present study used a Dlg~scan Ammal Activity Momtor to measure six &fferent aspects of spontaneous motor behavior in male CF-1 mice The Dlgtscan system uses infrared beams and computer analysis to quantify various behavioral vanables The mice were tested for 1 hour on 2 &fferent days of the week for 3 consecutwe weeks Both the temporal changes in the measured variables and the test-retest rehabdltles were examined in a group of 30 mice Statistical analysis of the data revealed slgmficantly higher mean values for total movement t~me, average &stance travelled, and horizontal activity on the first test session relative to the second session (p<0 01) The other 3 measures, total d~stance travelled, number of movements, and average speed, &d not vary significantly across test sessions All 6 behavioral variables showed good test-retest rehabdltles and these could be increased by aggregating the data on a weekly bas~s The present results indicate that the measures obtained from the Dlglscan system are rehable and that the ammals should first be habituated to the test apparatus in order to obtain stable basehne achvlty values Motor activity Open-field Automated monitor Rehabdltles Aggregation Time course Mice D~g~scan

Neuroscience Letters, 1987

Key wore£v Blood brain barrier; Freeze fracture; Protein tracer; Magnetic resonance imaging (MRI)... more Key wore£v Blood brain barrier; Freeze fracture; Protein tracer; Magnetic resonance imaging (MRI); Nuclear magnetic resonance imaging (NMR); Rat Exposure to a short (23.2 min) standard clinical magnetic resonance imaging (MRI) procedure elicits a temporary dysfunction of the blood brain barrier in rats. Monitoring of the increased permeability o1 rat brain frontal cortex microvessels with the protein tracer horseradish peroxidase and freeze-fracture electron microscopy, revealed an amplified vesicle-mediated transport of tracer across the microvessel cndothelium Io the albuminal basal lamina and extracellular compartment of the brain parenchyma. Recovery of normal blood brain function, as evidenced by exclusion of protein tracer from subendothelial basal lamina and neuropil extracellular milieu, was complete 15 30 min following cessation of the MRI exposure. These findings raise the possibility that exposure to clinical MRI procedures may also temporarily alter central blood brain permeability in human subjects. Magnetic resonance imaging (MRI) is a powerful noninvasive diagnostic procedure that is gaining rapid clinical acceptance [2]. The imaging procedure entails the concurrent exposure of subjects to a high-intensity static field, a radiofrequency field and time-varying magnetic field [5]. Although there is substantial literature to indicate that magnetic fields can affect a variety of biobehavioral functions [I, 9 12, 14, 15, 19, 25], relatively little is known regarding the possible behavioral and physiological effects of MRI-associated magnetic fields.

Neuroscience & Biobehavioral Reviews, 1998

The search for the cellular processes that underlie information storage within neuronal systems l... more The search for the cellular processes that underlie information storage within neuronal systems lead to the development of two models of post-activation potentiation, long-term potentiation (LTP) and kindling. Both models give rise to a long-lasting increase in synaptic strength and altered unit discharge patterns. The present paper reviews synaptic plasticity in the neocortex of awake freely moving rats following both single and multiple sessions of activation with high-frequency, tetanic electrical stimulation. The phenomenology of neocortical post-activation potentiation and some possible underlying mechanisms are discussed. We speculate that the functional significance of potentiated responses may reflect a reorganization of the neocortex in a manner similar to those that create and define receptive fields.