Same old: November 2007

Wednesday 28 November 2007

Embodying Cultured Networks with a Robotic Drawing Arm.

Embodying Cultured Networks with a Robotic Drawing Arm.

Conf Proc IEEE Eng Med Biol Soc. 2007;1:2996-2999

Authors: Bakkum DJ, Chao ZC, Gamblen P, Ben-Ary G, Shkolnik AG, Demarse TB, Potter SM

The advanced and robust computational power of the brain is shown by the complex behaviors it produces. By embodying living cultured neuronal networks with a robotic or simulated animal (animat) and situating them within an environment, we study how the basic principles of neuronal network communication can culminate into adaptive goal-directed behavior. We engineered a closed-loop biological-robotic drawing machine and explored sensory-motor mappings and training. Preliminary results suggest that real-time performance-based feedback allowed an animat to draw in desired directions. This approach may help instruct the future design of artificial neural systems and of the algorithms to interface sensory and motor prostheses with the brain.

PMID: 18002625 [PubMed - as supplied by publisher]

How do TTX and AP5 affect the post-recovery neuronal network activity synchronization?

How do TTX and AP5 affect the post-recovery neuronal network activity synchronization?

Conf Proc IEEE Eng Med Biol Soc. 2007;1:3012-3015

Authors: Esposti F, Signorini MG, Lamanna J, Gullo F, Wanke E

A lot of methods were created in last decade for the spatio-temporal analysis of multi-electrode array (MEA) neuronal data sets. The greater part of these methods does not consider the network as a whole but performs an analysis channel by channel. In this paper we illustrate how a very simple approach that considers the total network activity, is able to show interesting neuronal network features. In particular we perform two different analyses: a connectivity examination studying networks at different days in vitro and an analysis of the long period effects of the administration of two common neuro-active drugs, i.e. TTX and AP5. Our analysis is performed considering burst topology, i.e. cataloguing network bursts as Global (if they involve more than the 25% of the MEA channels) or Local (if less that 25%). This division allows, in the first analysis, to understand the network connectivity (increasing from div 1 to 6) and decreasing till reaching a plateau (from div 6 to 10). The second analysis highlights a substantial difference between the long period effects of TTX and AP5. While TTX induces a massive Global activity explosion, sign of a prolonged inhibitory synapse depression, AP5 shows only a modest Local activity increase, mark of the low effect of NMDA receptors on a mature neuronal network without inputs.

PMID: 18002629 [PubMed - as supplied by publisher]

Different cannabinoids exhibit different electrophysiological properties.

Different cannabinoids exhibit different electrophysiological properties.

NIDA Res Monogr. 1987;79:67-81

Authors: Turkanis SA, Karler R

PMID: 3125481 [PubMed - indexed for MEDLINE]

Marijuana use and the risk of new onset seizures.

Marijuana use and the risk of new onset seizures.

Trans Am Clin Climatol Assoc. 1992;103:176-81

Authors: Brust JC, Ng SK, Hauser AW, Susser M

PMID: 1413377 [PubMed - indexed for MEDLINE]

Blogged with Flock

[Results of a standardized survey on the medical use of cannabis products in the German-speaking area]

[Results of a standardized survey on the medical use of cannabis products in the German-speaking area]

Forsch Komplementarmed. 1999 Oct;6 Suppl 3:28-36

Authors: Schnelle M, Grotenhermen F, Reif M, Gorter RW

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 70s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation an increasing number of patients practices a self-prescription with cannabis products for relieving a variety of symptoms. An anonymous standardized survey of the medical use of cannabis and cannabis products of patients in Germany, Austria and Switzerland was conducted by the Association for Cannabis as Medicine (Cologne, Germany). During about one year 170 subjects participated in this survey; questionnaires of 128 patients could be included into the evaluation. 68% of these participants were males, 32% females, with a total mean age of 37.5 (+/- 9.6) years. The most frequently mentioned indications for medicinal cannabis use were depression (12.0%), multiple sclerosis (10.8%), HIV-infection (9.0%), migraine (6.6%), asthma (6.0%), back pain (5.4%), hepatitis C (4. 8%), sleeping disorders (4.8%), epilepsy (3.6%), spasticity (3.6%), headache (3.6%), alcoholism (3.0%), glaucoma (3.0%), nausea (3.0%), disk prolapse (2.4%), and spinal cord injury (2.4%). The majority of patients used natural cannabis products such as marihuana, hashish and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription. About half of the 128 participants of the survey (52.4%) had used cannabis as a recreational drug before the onset of their illness. To date 14.3% took cannabis orally, 49.2% by inhalation and in 36.5% of cases both application modes were used. 72.2% of the patients stated the symptoms of their illness to have 'much improved' after cannabis ingestion, 23.4% stated to have 'slightly improved', 4.8% experienced 'no change' and 1.6% described that their symptoms got 'worse'. Being asked for the satisfaction with their therapeutic use of cannabis 60.8% stated to be 'very satisfied', 24.0% 'satisfied', 11.2% 'partly satisfied' and 4.0% were 'not satisfied'. 70.8% experienced no side effects, 26.4% described 'moderate' and 3.3% 'strong' side effects. 84.1% of patients have not felt any need for dose escalation during the last 3 months, 11.0% had to increase their cannabis dose 'moderately' and 4.8% 'strongly' in order to maintain the therapeutic effects. Thus, this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects. Because the patient group responding to this survey is presumably highly selected, no conclusions can be drawn about the quantity of wanted and unwanted effects of the medicinal use of the hemp plant for particular indications. Copyright Copyright 1999 S. Karger GmbH, Freiburg

PMID: 10575286 [PubMed - indexed for MEDLINE]

Therapeutic aspects of cannabis and cannabinoids.

Therapeutic aspects of cannabis and cannabinoids.

Br J Psychiatry. 2001 Feb;178:107-15

Authors: Robson P

BACKGROUND: Review commissioned in 1996 by the Department of Health (DOH). AIMS: Assess therapeutic profile of cannabis and cannabinoids. METHOD: Medline search, references supplied by DOH and others, and personal communications. RESULTS AND CONCLUSIONS: Cannabis and some cannabinoids are effective anti-emetics and analgesics and reduce intra-ocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.

PMID: 11157423 [PubMed - indexed for MEDLINE]

Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice.

Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice.

Epilepsia. 2001 Mar;42(3):321-7

Authors: Lambert DM, Vandevoorde S, Diependaele G, Govaerts SJ, Robert AR

PURPOSE: The purpose of this study was to evaluate in mice the anticonvulsant potential of N-palmitoylethanolamide, a putative endocannabinoid that accumulates in the body during inflammatory processes. METHODS: N-palmitoylethanolamide was injected intraperitoneally (i.p.) in mice and evaluated for anticonvulsant activity [in maximal electroshock seizure (MES) and chemical-induced convulsions] and for neurologic impairment (rotorod). It was compared with anandamide and with different palmitic acid analogues as well as with reference anticonvulsants (AEDs) injected under the same conditions. RESULTS: The MES test showed, after i.p. administration to mice, that N-palmitoy]ethanolamide had an median effective dose (ED50) value comparable to that of phenytoin (PHT; 8.9 and 9.2 mg/kg, respectively). In the subcutaneous pentylenetetrazol test and in the 3-mercaptropropionic acid test, it was effective only against tonic convulsions. N-palmitoylethanolamide was devoid of neurologic impairment < or = 250 mg/kg, yielding a high protective index. CONCLUSIONS: N-palmitoylethanolamide, an endogenous compound with antiinflammatory and analgesic activities, is a potent AED in mice. Its precise mechanism of action remains to be elucidated.

PMID: 11442148 [PubMed - indexed for MEDLINE]

Direct inhibition of T-type calcium channels by the endogenous cannabinoid anandamide.

Direct inhibition of T-type calcium channels by the endogenous cannabinoid anandamide.

EMBO J. 2001 Dec 17;20(24):7033-40

Authors: Chemin J, Monteil A, Perez-Reyes E, Nargeot J, Lory P

Low-voltage-activated or T-type Ca(2+) channels (T-channels) are widely expressed, especially in the central nervous system where they contribute to pacemaker activities and are involved in the pathogenesis of epilepsy. Proper elucidation of their cellular functions has been hampered by the lack of selective pharmacology as well as the absence of generic endogenous regulations. We report here that both cloned (alpha(1G), alpha(1H) and alpha(1I) subunits) and native T-channels are blocked by the endogenous cannabinoid, anandamide. Anandamide, known to exert its physiological effects through cannabinoid receptors, inhibits T-currents independently from the activation of CB1/CB2 receptors, G-proteins, phospholipases and protein kinase pathways. Anandamide appears to be the first endogenous ligand acting directly on T-channels at submicromolar concentrations. Block of anandamide membrane transport by AM404 prevents T-current inhibition, suggesting that anandamide acts intracellularly. Anandamide preferentially binds and stabilizes T-channels in the inactivated state and is responsible for a significant decrease of T-currents associated with neuronal firing activities. Our data demonstrate that anandamide inhibition of T-channels can regulate neuronal excitability and account for CB receptor-independent effects of this signaling molecule.

PMID: 11742980 [PubMed - indexed for MEDLINE]

Psychostimulants and epilepsy.

Psychostimulants and epilepsy.

Epilepsia. 2002;43 Suppl 2:28-31

Authors: Zagnoni PG, Albano C

PURPOSE: The aim of this article is to review the literature on the effects of psychostimulants in epileptic subjects in order to reach a consensus statement regarding the use or abuse of these substances. METHODS: Psychostimulant substances have been considered the drugs that share the ability to produce excitation of the CNS leading to convulsions. The stimulation may be at cortical, brainstem, or spinal levels. In this article, the following cortical stimulants are analyzed and discussed: cocaine, amphetamine and related agents, caffeine, cannabinoids, and psychedelic drugs. This review is based on research done using pharmacological textbooks and Medline. RESULTS: The use of cocaine is associated with the occurrence of seizures. The reported frequency varies from 1% to 40% of addicted subjects, based on the typology of the considered study. Amphetamines and related drugs rarely induce epileptic seizures at therapeutic doses, but seizures may occur after the first dosing. Caffeine at high doses may induce epileptic seizures because of its adenosine receptor-antagonizing properties. Marijuana, at variance with other psychostimulants, owing to its serotonin-mediated anticonvulsant action, could have a medical use for the treatment of epilepsy. Psychedelic compounds rarely induce epileptic seizures, but the most common clinical CNS complication after ingestion of ecstasy is the occurrence of seizures. CONCLUSIONS: The use of psychostimulants, except for marijuana, can induce single or multiple seizures in healthy subjects.

PMID: 11903480 [PubMed - indexed for MEDLINE]

Medical efficacy of cannabinoids and marijuana: a comprehensive review of the literature.

Medical efficacy of cannabinoids and marijuana: a comprehensive review of the literature.

J Palliat Care. 2002;18(2):111-22

Authors: Bagshaw SM, Hagen NA

PMID: 12164099 [PubMed - indexed for MEDLINE]

Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity.

Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity.

Eur J Pharmacol. 2002 Oct 11;452(3):295-301

Authors: Wallace MJ, Martin BR, DeLorenzo RJ

The anticonvulsant effect of cannabinoids has been shown to be mediated through activation of the cannabinoid CB(1) receptor. This study was initiated to evaluate the effects of endogenously occurring cannabinoids (endocannabinoids) on seizure severity and threshold. The anticonvulsant effect of the endocannabinoid, arachidonylethanolamine (anandamide), was evaluated in the maximal electroshock seizure model using male CF-1 mice and was found to be a fully efficacious anticonvulsant (ED(50)=50 mg/kg i.p.). The metabolically stable analog of anandamide, (R)-(20-cyano-16,16-dimetyldocosa-cis-5,8,11,14-tetraenoyl)-1'-hydroxy-2'-propylamine (O-1812), was also determined to be a potent anticonvulsant in the maximal electroshock model (ED(50)=1.5 mg/kg i.p.). Furthermore, pretreatment with the cannabinoid CB(1) receptor specific antagonist N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A) completely abolished the anticonvulsant effect of anandamide as well as O-1812 (P< or =0.01, Fisher exact test), indicating a cannabinoid CB(1) receptor-mediated anticonvulsant mechanism for both endocannabinoid compounds. Additionally, the influence of cannabinoid CB(1) receptor endogenous tone on maximal seizure threshold was assessed using SR141716A alone. Our data show that SR141716A (10 mg/kg i.p.) significantly reduced maximal seizure threshold (CC(50)=14.27 mA) compared to vehicle-treated animals (CC(50)=17.57 mA) (potency ratio=1.23, lower confidence limit=1.06, upper confidence limit=1.43), indicating the presence of an endogenous cannabinoid tone that modulates seizure activity. These data demonstrate that anandamide and its analog, O-1812, are anticonvulsant in a whole animal model and further implicate the cannabinoid CB(1) receptor as a major endogenous site of seizure modulation.

PMID: 12359270 [PubMed - indexed for MEDLINE]

Cannabinoid receptor-1 activation suppresses inhibitory synaptic activity in human dentate gyrus.

Cannabinoid receptor-1 activation suppresses inhibitory synaptic activity in human dentate gyrus.

Neuropharmacology. 2003 Jul;45(1):116-21

Authors: Nakatsuka T, Chen HX, Roper SN, Gu JG

In spite of their popular uses as recreational drugs and their potential therapeutic uses, little direct information has been obtained about the synaptic effects of cannabinoids in the human brain. In the present study, patch-clamp recordings were performed on granule cells of the human dentate gyrus and the effects of cannabinoid receptor-1 (CB1) activation on inhibitory synaptic activity were examined. Activation of CB1 receptors by WIN55212-2 significantly suppressed both frequency and amplitude of spontaneous inhibitory synaptic currents (IPSCs) to about 50% of control. The suppressive effects were completely abolished in the presence of the CB1 receptor antagonist, AM251. WIN55212-2 also suppressed evoked IPSCs. However, neither frequency nor amplitude of miniature IPSCs were affected by WIN55212-2. These results provide electrophysiological evidence for the role of CB1 receptors in modulating inhibitory activity in human dentate gyrus.

PMID: 12814664 [PubMed - indexed for MEDLINE]

Hedonic-specific activity in piriform cortex during odor imagery mimics that during odor perception.

Hedonic-specific activity in piriform cortex during odor imagery mimics that during odor perception.

J Neurophysiol. 2007 Oct 3;

Authors: Bensafi M, Sobel N, Khan RM

Whereas it is known that visual imagery is accompanied by activity in visual cortical areas, including primary visual cortex, whether olfactory imagery exists remains controversial. Here we asked whether cue-dependent olfactory imagery was similarly accompanied by activity in olfactory cortex, and in particular whether hedonic-specific patterns of activity evident in olfactory perception would also be present during olfactory imagery. We used functional magnetic resonance imaging to measure activity in subjects who alternated between smelling and imagining pleasant and unpleasant odors. Activity induced by imagining odors mimicked that induced by perceiving real odorants, not only in the particular brain regions activated, but also in its hedonic-specific pattern. For both real and imagined odors, unpleasant stimuli induced greater activity than pleasant stimuli in the left frontal portion of piriform cortex and left insula. These findings combine with findings from other modalities to suggest activation of primary sensory cortical structures during mental imagery of sensory events.

PMID: 17913994 [PubMed - as supplied by publisher]

Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

Neuroimage. 2007 Sep 14;

Authors: Ciumas C, Lindström P, Bernard A, Savic I

Metabolic and neuro-receptor abnormalities within the extrafocal limbic circuits are established in mesial temporal lobe epilepsy (MTLE). However, very little is known about how these circuits process external stimuli. We tested whether odor activation can help delineate limbic functional disintegration in MTLE, and measured cerebral blood flow with PET during birhinal smelling of familiar and unfamiliar odors, using smelling of odorless air as the baseline condition. Patients with MTLE (13 left-sided, 10 right-sided) and 21 controls were investigated. In addition to odor activation, the analysis included functional connectivity, using right and left piriform cortex as seed regions. Healthy controls activated the amygdala, piriform, anterior insular, and cingulate cortices on both sides. Smelling of familiar odors engaged, in addition, the right parahippocampus, and the left Brodmann Area (BA) 44, 45, 47. Patients failed to activate the amygdala, piriform and the anterior insular cortex in the epileptogenic hemisphere. Furthermore, those with left MTLE did not activate the left BA 44, 45 and 47 with familiar odors, which they perceived as less familiar than controls. Congruent with the activation data each seed region was in patients functionally disconnected with the contralateral amygdala+piriform+insular cortex. The functional disintegration in patients exceeded the reduced activation, and included the contralateral temporal neocortex, and in subjects with right MTLE also the right orbitofrontal cortex. Imaging of odor perception may be used to delineate functional disintegration of the limbic networks in MTLE. It shows an altered response in several regions, which may underlie some interictal behavioral problems associated with this condition.

PMID: 17951077 [PubMed - as supplied by publisher]

Thursday 15 November 2007

Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy.

Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy.

J Neurosci. 2007 Sep 12;27(37):9866-73

Authors: Huberfeld G, Wittner L, Clemenceau S, Baulac M, Kaila K, Miles R, Rivera C

Changes in chloride (Cl-) homeostasis may be involved in the generation of some epileptic activities. In this study, we asked whether Cl- homeostasis, and thus GABAergic signaling, is altered in tissue from patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis. Slices prepared from this human tissue generated a spontaneous interictal-like activity that was initiated in the subiculum. Records from a minority of subicular pyramidal cells revealed depolarizing GABA(A) receptor-mediated postsynaptic events, indicating a perturbed Cl- homeostasis. We assessed possible contributions of changes in expression of the potassium-chloride cotransporter KCC2. Double in situ hybridization showed that mRNA for KCC2 was absent from approximately 30% of CaMKIIalpha (calcium/calmodulin-dependent protein kinase IIalpha)-positive subicular pyramidal cells. Combining intracellular recordings with biocytin-filled electrodes and KCC2 immunochemistry, we observed that all cells that were hyperpolarized during interictal events were immunopositive for KCC2, whereas the majority of depolarized cells were immunonegative. Bumetanide, at doses that selectively block the chloride-importing potassium-sodium-chloride cotransporter NKCC1, produced a hyperpolarizing shift in GABA(A) reversal potentials and suppressed interictal activity. Changes in Cl- transporter expression thus contribute to human epileptiform activity, and molecules acting on these transporters may be useful antiepileptic drugs.

PMID: 17855601 [PubMed - indexed for MEDLINE]

Chaos, brain and divided consciousness.

Chaos, brain and divided consciousness.

Acta Univ Carol Med Monogr. 2007;153:9-80

Authors: Bob P

Modern trends in psychology and cognitive neuroscience suggest that applications of nonlinear dynamics, chaos and self-organization seem to be particularly important for research of some fundamental problems regarding mind-brain relationship. Relevant problems among others are formations of memories during alterations of mental states and nature of a barrier that divides mental states, and leads to the process called dissociation. This process is related to a formation of groups of neurons which often synchronize their firing patterns in a unique spatial maner. Central theme of this study is the relationship between level of moving and oscilating mental processes and their neurophysiological substrate. This opens a question about principles of organization of conscious experiences and how these experiences arise in the brain. Chaotic self-organization provides a unique theoretical and experimental tool for deeper understanding of dissociative phenomena and enables to study how dissociative phenomena can be linked to epileptiform discharges which are related to various forms of psychological and somatic manifestations. Organizing principles that constitute human consciousness and other mental phenomena from this point of view may be described by analysis and reconstruction of underlying dynamics of psychological or psychophysiological measures. These nonlinear methods in this study were used for analysis of characteristic changes in EEG and bilateral electrodermal activity (EDA) during reliving of dissociated traumatic and stressful memories and during psychopathological states. Analysis confirms a possible role of chaotic transitions in the processing of dissociated memory. Supportive finding for a possible chaotic process related to dissociation found in this study represent also significant relationship of dissociation, epileptiform discharges measured by typical psychopathological manifestations and characteristic laterality changes in bilateral EDA in patients with schizophrenia and depression. Increased level of psychopathological symptoms indicates close relationship to the right-left EDA asymmetry and asymmetry of information entropy calculated by non-linear recurrence quantification analysis of EDA records. Because epileptiform activity has specific chaotic behaviour and calculated information entropy from EDA records reflects the complexity of the deterministic structure in the system there is a relevant assumption that unilaterally increased complexity may produce interhemispheric disbalance and increased chaoticity which hypothetically may serve as a dynamic source of epileptiform discharges related to trauma induced kindling mechanism. Specific form of chaotic inner organization which cannot be explained only as a consequence of external causality support also psychophysiological data that lead to the so-called self-organizing theory of dreaming by Kahn and Hobson. This study suggests that self-organizing theory of dreaming is particularly important with respect to problem of memory formation and processing during dissociative states characteristic for dreams. Recent data and also findings of this study support the research utility of chaos theory in psychology and neuroscience, and also its conceptual view of dynamic ordering factors and self-organization underlying psychological processes and brain physiology.

PMID: 17867519 [PubMed - indexed for MEDLINE]

Enhanced astrocytic Ca2+ signals contribute to neuronal excitotoxicity after status epilepticus.

Enhanced astrocytic Ca2+ signals contribute to neuronal excitotoxicity after status epilepticus.

J Neurosci. 2007 Oct 3;27(40):10674-84

Authors: Ding S, Fellin T, Zhu Y, Lee SY, Auberson YP, Meaney DF, Coulter DA, Carmignoto G, Haydon PG

Status epilepticus (SE), an unremitting seizure, is known to cause a variety of traumatic responses including delayed neuronal death and later cognitive decline. Although excitotoxicity has been implicated in this delayed process, the cellular mechanisms are unclear. Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca2+ signaling and because these signals are able to induce the release of the excitotoxic transmitter glutamate from these glia, we asked whether astrocytes are activated during status epilepticus and whether they contribute to delayed neuronal death in vivo. Using two-photon microscopy in vivo, we show that status epilepticus enhances astrocytic Ca2+ signals for 3 d and that the period of elevated glial Ca2+ signaling is correlated with the period of delayed neuronal death. To ask whether astrocytes contribute to delayed neuronal death, we first administered antagonists which inhibit gliotransmission: MPEP [2-methyl-6-(phenylethynyl)pyridine], a metabotropic glutamate receptor 5 antagonist that blocks astrocytic Ca2+ signals in vivo, and ifenprodil, an NMDA receptor antagonist that reduces the actions of glial-derived glutamate. Administration of these antagonists after SE provided significant neuronal protection raising the potential for a glial contribution to neuronal death. To test this glial hypothesis directly, we loaded Ca2+ chelators selectively into astrocytes after status epilepticus. We demonstrate that the selective attenuation of glial Ca2+ signals leads to neuronal protection. These observations support neurotoxic roles for astrocytic gliotransmission in pathological conditions and identify this process as a novel therapeutic target.

PMID: 17913901 [PubMed - in process]

A pilot study transitioning children onto levetiracetam monotherapy to improve language dysfunction associated with benign rolandic epilepsy.

A pilot study transitioning children onto levetiracetam monotherapy to improve language dysfunction associated with benign rolandic epilepsy.

Epilepsy Behav. 2007 Oct 11;

Authors: Kossoff EH, Los JG, Boatman DF

Benign rolandic epilepsy (BRE) and Landau-Kleffner syndrome (LKS) are similar epilepsy syndromes with sleep-accentuated epileptiform activity, sporadic seizures, and language dysfunction. Levetiracetam has been associated with improved language function in LKS and seizure reduction in BRE. We hypothesized levetiracetam would improve language function in children with BRE. A pilot study was performed with six children (aged 6-12) with BRE and evidence of impaired auditory comprehension and verbal memory. Children were transitioned from their current anticonvulsant to 40 mg/kg/day levetiracetam over a 2-week period and retested at 6 months. At 6 months, three of four children with baseline auditory comprehension impairments performed normally (P=0.06), and five had improved auditory verbal memory (P=0.08). Seizures improved in five, decreasing from 2.7 to 1.0 seizure per 6 months (P=0.11). Results from this pilot study suggest that levetiracetam may have a beneficial effect on language in children with BRE.

PMID: 17936689 [PubMed - as supplied by publisher]

Inhibitory interneurons in the piriform cortex.

Inhibitory interneurons in the piriform cortex.

Clin Exp Pharmacol Physiol. 2007 Oct;34(10):1064-9

Authors: Suzuki N, Bekkers JM

1. The piriform cortex (PC) is the largest subdivision of the olfactory cortex and the first cortical destination of olfactory information. Despite the relatively simple anatomy of the PC and its obvious appeal as a model system for the study of cortical sensory processing, there are many outstanding questions about its basic cell physiology. In the present article, we review what is known about GABAergic inhibitory interneurons in the PC. 2. The GABA-containing neurons in the PC are morphologically diverse, ranging from small neurogliaform cells to large multipolar forms. Some of these classes are distributed across all three main layers of the PC, whereas others have a more restricted laminar expression. 3. Distinct and overlapping populations of GABAergic basket cells in Layers II and III of the PC express different combinations of calcium-binding proteins and neuropeptides. Few Layer I interneurons express any of the molecular markers so far examined. 4. The intrinsic firing properties of one or two types of putative PC interneurons have been measured and inhibitory post-synaptic responses have been recorded in PC pyramidal cells following extracellular stimulation. However, little is known about the physiology of the subtypes of interneurons identified. 5. In view of the likely importance of PC interneurons in olfactory learning, olfactory coding and epileptogenesis, further investigation of their properties is likely to be highly informative.

PMID: 17714095 [PubMed - indexed for MEDLINE]

Early Telencephalic Migration Topographically Converging in the Olfactory Cortex.

Early Telencephalic Migration Topographically Converging in the Olfactory Cortex.

Cereb Cortex. 2007 Sep 17;

Authors: García-Moreno F, López-Mascaraque L, de Carlos JA

Neurons that participate in the olfactory system arise in different areas of the developing mouse telencephalon. The generation of these different cell populations and their tangential migration into the olfactory cortex (OC) was tracked by tracer injection and in toto embryo culture. Cells originating in the dorsal lateral ganglionic eminence (LGE) migrate tangentially along the anteroposterior axis to settle in the piriform cortex (PC). Those originating in the ventral domain of this structure occupy the thickness of the olfactory tubercle (OT), whereas cells from the rostral LGE migrate tangentially into the most anterior telencephalon, at the level of the prospective olfactory bulb (pOB). Neurons from the dorsal telencephalon migrate ventrally, bordering the PC, toward olfactory structures. Two cell populations migrate tangentially from the rostromedial telencephalic wall to the OT and the PC, passing through the ventromedial and dorsolateral face of the telencephalon. Some cells from the germinative area of the rostral telencephalon, at the level of the septoeminential sulcus, migrate rostrally to the pOB or caudally to the OC. Thus, we demonstrate multiple telencephalic origins for the first olfactory neurons and each population following different migratory routes to colonize the OC according to an accurate topographic map.

PMID: 17878174 [PubMed - as supplied by publisher]

Distinct effects of anterior pyriform cortex and the lateral hypothalamus lesions on protein intake in rats.

Distinct effects of anterior pyriform cortex and the lateral hypothalamus lesions on protein intake in rats.

J Med Invest. 2007 Aug;54(3-4):255-60

Authors: Nakao R, Ozaki E, Hasegawa M, Kondo A, Uezu K, Hirasaka K, Nikawa T, Kishi K

Several specific locations in brain, including pyriform cortex and hypothalamus, are associated with regulation of food intake. Although lesions of these locations significantly alter food intake, their involvement in the selection of macronutrients is not well characterized. In this study, we examined distinct effects of anterior pyriform cortex (APC) and lateral hypothalamus (LH) lesions on protein intake in rats. The APC or LH of male adult rats were lesioned by treatment with kainic acid, and the rats were then given free access to two kinds of casein diets containing high (60%) and low (5%) protein. Total energy content of these diets was kept constant by changing the carbohydrate content. Following the APC lesions, body weight and food intake decreased, but returned to control levels on day 13 and day 4, respectively. APC lesions did not change the ratio of protein intake. In contrast, LH lesions disturbed body weight gain and the selection of a high protein diet for at least two weeks, although food intake returned to control levels by day 2. Our results suggest that LH, but not APC, may play an important role in the selection of protein intake in rats.

PMID: 17878674 [PubMed - indexed for MEDLINE]

Muscarinic receptor activation modulates granule cell excitability and potentiates inhibition onto mitral cells in the rat olfactory bulb.

Muscarinic receptor activation modulates granule cell excitability and potentiates inhibition onto mitral cells in the rat olfactory bulb.

J Neurosci. 2007 Oct 10;27(41):10969-81

Authors: Pressler RT, Inoue T, Strowbridge BW

The olfactory bulb is a second-order brain region that connects sensory neurons with cortical areas. However, the olfactory bulb does not appear to play a simple relay role and is subject instead to extensive local and extrinsic synaptic influences. Prime among the external, or centrifugal, inputs is the dense cholinergic innervation from the basal forebrain, which terminates in both the granule cell and plexiform layers. Cholinergic inputs to the bulb have been implicated in olfactory working memory tasks in rodents and may be related to olfactory deficits reported in people with neurodegenerative disorders that involve basal forebrain neurons. In this study, we use whole-cell recordings from acute rat slices to demonstrate that one function of this input is to potentiate the excitability of GABAergic granule cells and thereby modulate inhibitory drive onto mitral cells. This increase in granule cell excitability is mediated by a concomitant decrease in the normal afterhyperpolarization response and augmentation of an afterdepolarization, both triggered by pirenzepine-sensitive M1 receptors. The afterdepolarization was dependent on elevations in intracellular calcium and appeared to be mediated by a calcium-activated nonselective cation current (I(CAN)). Near firing threshold, depolarizing inputs could evoke quasipersistent firing characterized by irregular discharges that lasted, on average, for 2 min. In addition to regulating the excitability of the primary interneuronal subtype in the bulb, M1 receptors regulate the degree of adaptation that occurs during repetitive sniffing-like inputs and may therefore play a critical role in regulating short-term plasticity in the olfactory system.

PMID: 17928438 [PubMed - indexed for MEDLINE]

Same old