The Role of the Piriform Cortex in Kindling

Löscher, Wolfgang; Ebert, Ulrich

doi:10.1016/s0301-0082(96)00036-6

Cited by 272 publications

(215 citation statements)

References 180 publications

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“…This is another piece of data suggesting that the frontal cortex may be a critical brain region for d-opioid receptor-mediated antidepressant behavioral effects, whereas, the olfactory cortex is only responsive to convulsions and may mediate convulsive effects. The amygdala, primary olfactory cortex, and endopiriform nucleus have been implicated in seizure propagation in amygdala kindling models of epilepsy (Loscher and Ebert, 1996). The data presented here suggest that d-opioid receptor-mediated convulsions may involve this amygdala-olfactory cortex circuit.…”

Section: Tolerance Development To Increases In Bdnf Mrnamentioning

confidence: 57%

The δ-Opioid Receptor Agonist (+)BW373U86 Regulates BDNF mRNA Expression in Rats

Torregrossa

Isgor

Folk

et al. 2003

Neuropsychopharmacol

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d-Opioid receptor agonists have antidepressant-like effects in behavioral models of depression. Chronic administration of classical antidepressants upregulates mRNA expression of brain-derived neurotrophic factor (BDNF) and its high-affinity tyrosine kinase receptor, TrkB in the frontal cortex and hippocampus of rats. Increases in BDNF and TrkB levels are thought to be important for the therapeutic effects of these drugs. Therefore, we examined the ability of the d-opioid receptor agonist (+)BW373U86 to regulate BDNF and TrkB mRNA expression in frontal cortex, hippocampus, as well as, basolateral amygdala, endopiriform nucleus, and primary olfactory cortex. At 3 h after a single administration of (+)BW373U86 animals were killed and BDNF and TrkB mRNA levels were examined by in situ hybridization. BDNF mRNA levels produced by (+)BW373U86 were compared to acute administration of the antidepressants desipramine and bupropion. A behaviorally antidepressant dose of 10 mg/kg (+)BW373U86 increased BDNF mRNA expression in all regions examined; a smaller dose of (+)BW373U86 (1 mg/kg) significantly increased BDNF mRNA expression only in frontal cortex. The d-opioid receptor antagonist naltrindole blocked (+)BW373U86-mediated increases in BDNF mRNA expression. In addition, tolerance developed to increased BDNF mRNA expression with repeated injection, except in frontal cortex. Midazolam was administered to some animals to prevent the convulsions produced by (+)BW373U86, but midazolam did not block d-opioid receptormediated increases in BDNF mRNA expression in frontal cortex, hippocampus, or amygdala. Unlike desipramine and bupropion, (+)BW373U86 upregulated BDNF mRNA expression acutely (within 3 h after a single administration). These data support the concept that d-opioid receptor agonists may have antidepressant potential, and could be good targets for the development of faster-acting antidepressants.

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Section: Tolerance Development To Increases In Bdnf Mrnamentioning

confidence: 57%

The δ-Opioid Receptor Agonist (+)BW373U86 Regulates BDNF mRNA Expression in Rats

Torregrossa

Isgor

Folk

et al. 2003

Neuropsychopharmacol

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“…Because the piriform cortex plays an important role in the transition from focal to generalized seizures during kindling epileptogenesis (55,56), increased galanin levels in this area could contribute to the suppression of kindling development in GalOE mice. The galanin-LI in the piriform cortex could be located either in the distal apical dendrites of the pyramidal cells or in the nerve terminals originating from the olfactory bulb mitral cells, which innervate these dendrites (57).…”

Section: Resultsmentioning

confidence: 99%

Suppressed kindling epileptogenesis in mice with ectopic overexpression of galanin

Kokaia

Holmberg

Nanobashvili

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

103

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The neuropeptide galanin has been shown to suppress epileptic seizures. In cortical and hippocampal areas, galanin is normally mainly expressed in noradrenergic afferents. We have generated a mouse overexpressing galanin in neurons under the plateletderived growth factor B promoter. RIA and HPLC analysis revealed up to 8-fold higher levels of galanin in transgenic as compared with wild-type mice. Ectopic galanin overexpression was detected especially in dentate granule cells and hippocampal and cortical pyramidal neurons. Galanin-overexpressing mice showed retardation of seizure generalization during hippocampal kindling, a model for human complex partial epilepsy. The high levels of galanin in mossy fibers found in the transgenic mice were further increased after seizures. Frequency facilitation of field excitatory postsynaptic potentials, a form of short-term synaptic plasticity assessed in hippocampal slices, was reduced in mossy fiber-CA3 cell synapses of galanin-overexpressing mice, indicating suppressed glutamate release. This effect was reversed by application of the putative galanin receptor antagonist M35. These data provide evidence that ectopically overexpressed galanin can be released and dampen the development of epilepsy by means of receptor-mediated action, at least partly by reducing glutamate release from mossy fibers.G alanin, a 29-aa neuropeptide (1), is widely distributed throughout the rat brain (2, 3) and coexists with classic transmitters in several systems (4), with particularly high levels in noradrenergic locus coeruleus neurons (5, 6). Galanin-binding sites have been mapped (7,8), and three receptor subtypes, GalR1 (9-11), 49), and GalR3 (15), have been cloned. There is evidence for involvement of galanin in multiple neuronal functions (16,17), as also revealed in recent studies on transgenic mice (18)(19)(20).Many studies support an important role of neuropeptides in seizure activity (21)(22)(23). This role is true also for galanin. Thus, intrahippocampal injection of galanin during status epilepticus (SE) in rats has powerful anticonvulsant effects (24). In accordance with these data, mice overexpressing the galanin gene under the dopamine-␤-hydroxylase promoter, presumably in noradrenergic fibers, show increased resistance to SE and kainate-and pentylenetetrazol-evoked seizures (25). Conversely, administration of galanin antagonists, such as M35 (26), and targeted disruption of the galanin gene increase seizure susceptibility in these models (24,25). Taken together, available data indicate that galanin released from noradrenergic fibers (3, 5, 27) can suppress epileptic seizures. Although the underlying mechanisms are not known, it has been shown that galanin can inhibit glutamate release by means of activation of presynaptic ATP-dependent K ϩ channels (28).We speculated that galanin release from neurons not normally containing this neuropeptide, e.g., in the epileptic focus, might be necessary to optimize the seizure-suppressant action of galanin. To explore the functional conseque...

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“…The piriform cortex is a highly excitable region that extends over the ventrolateral forebrain in rodents (Galvan et al, 1982;Luskin and Price, 1983;Loscher and Ebert, 1996). This three-layered cortical area projects to several limbic structures including the amygdala, lateral entorhinal cortex, and subiculum (Luskin and Price, 1983;Haberly, 2001).…”

Section: Introductionmentioning

confidence: 99%

Neurosteroids modulate epileptiform activity and associated high-frequency oscillations in the piriform cortex

Herrington

Lévesque

2014

Neuroscience

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Allotetrahydrodeoxycorticosterone (THDOC) belongs to a class of pregnane neurosteroidal compounds that enhance brain inhibition by interacting directly with GABA A signaling, mainly through an increase in tonic inhibitory current. Here, we addressed the role of THDOC in the modulation of interictal-and ictal-like activity and associated high-frequency oscillations (HFOs, 80-500 Hz; ripples: 80-200 Hz, fast ripples: 250-500 Hz) recorded in vitro in the rat piriform cortex, a highly excitable brain structure that is implicated in seizure generation and maintenance. We found that THDOC: (i) increased the duration of interictal discharges in the anterior piriform cortex while decreasing ictal discharge duration in both anterior and posterior piriform cortices; (ii) reduced the occurrence of HFOs associated to both interictal and ictal discharges; and (iii) prolonged the duration of 4-aminopyridine-induced, glutamatergic independent synchronous field potentials that are known to mainly result from the activation of GABA A receptors. Our results indicate that THDOC can modulate epileptiform synchronization in the piriform cortex presumably by potentiating GABA A receptor-mediated signaling. This evidence supports the view that neurosteroids regulate neuronal excitability and thus control the occurrence of seizures.

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The Role of the Piriform Cortex in Kindling

Cited by 272 publications

References 180 publications

The δ-Opioid Receptor Agonist (+)BW373U86 Regulates BDNF mRNA Expression in Rats

The δ-Opioid Receptor Agonist (+)BW373U86 Regulates BDNF mRNA Expression in Rats

Suppressed kindling epileptogenesis in mice with ectopic overexpression of galanin

Neurosteroids modulate epileptiform activity and associated high-frequency oscillations in the piriform cortex

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