sfn2005

Buse JE, Kim I, Wilson RE, Wellman CL (2005) Contributions of NMDA receptors to cortical plasticity after cholinergic deafferentation. Neuroscience 2005 Abstracts 214.21. Society for Neuroscience, Washington, DC.

Summary: Plasticity of frontal cortex is altered in aging rats: lesions of the nucleus basalis magnocellularis (NBM) increase both expression of the AMPA receptor subunit GluR1 and dendritic spines in frontal cortex of young adult but not aging rats. Others have shown that NMDA receptors are reduced in aged cortex. Given the role of NMDA receptors in synaptic plasticity, altered transmission at NMDA receptors may be responsible for the differential cortical plasticity in aging rats. To begin to test this hypothesis, we assessed the effect of NMDA receptor blockade on GluR1 subunit expression and dendritic spine density on pyramidal cells in layer II-III of frontal cortex after either sham or 192 IgG saporin lesions of the NBM. Young adult rats received unilateral sham or 192 IgG saporin lesions of the NBM, along with subscapular implants of osmotic minipumps delivering either MK801 (6 mg/ml; 0.5 μl/h) or phosphate-buffered saline. Two weeks after surgery, rats were euthanized and brains were processed for either immunohistochemical labeling of GluR1 subunit protein or Golgi-Cox histology. To quantify GluR1 expression, an unbiased stereological technique was used to estimate the number of intensely labeled neurons. To quantify spine density, second- and third-order basilar dendrites of Golgi-stained pyramidal cells were drawn and spines were counted. NBM lesions significantly increased both GluR1 expression and spine density, by 83% and 28% respectively. While NMDA blockade alone had no effect, it prevented the lesion-induced increases in GluR1 expression and spine density. Thus, transmission at NMDA receptors may be necessary for synaptic plasticity after cholinergic deafferentation, and age-related changes in NMDA receptors may contribute to altered plasticity of frontal cortex of aging rats.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Furlong TM, Carrive P (2005) Hypocretin/orexin neurons and the perifornical hypothalamus play a more important role in contextual fear than in restraint stress. Neuroscience 2005 Abstracts 304.11. Society for Neuroscience, Washington, DC.

Summary: We investigated the role of the neuropeptide hypocretin (Hcrt; also known as orexin) in two different types of stress: conditioned fear to context and restraint stress. For contextual fear, male Wistar rats were tested by re-exposure to a chamber where electric footshocks had previously been administered. For restraint stress, the rats were restrained in tight Plexiglas tubes. In the first study, lesions of the perifornical region of the hypothalamus (PeF; where Hcrt neurons are located) were made with a Hcrt-saporin toxin prior to testing. The cardiovascular response was measured using radio-telemetry. The pressor and tachycardic responses to the context were reduced by 77% and 74% respectively, compared to an intact group (p<0.001, for both comparisons). The lesioned group also displayed significant reductions in freezing (by 67%) and ultrasonic vocalisations (by 74%). In contrast, the cardiovascular response to restraint stress did not differ between the two groups (p>0.5). In the second study, two hours after the tests, the rats were euthanased (200 mg/kg sodium pentobarbitone, i.p) and their brains removed and processed for double immunohistochemical detection of Hcrt and Fos. There was a higher percentage of Hcrt neurons double labeled with Fos after contextual fear (17%) than after restraint stress (6%), which indicates that more Hcrt neurons were active during contextual fear (p=0.024). These studies suggest that the PeF region and Hcrt neurons play a more important role in contextual fear than in restraint stress.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Gerashchenko D, Murillo-Rodriguez E, Blanco-Centurion C, Lin L, Nishino S, Mignot E, Shiromani PJ (2005) Adenosine levels do not increase with 6 h waking in rats with lesions of the lateral hypothalamus. Neuroscience 2005 Abstracts 63.9. Society for Neuroscience, Washington, DC.

Summary: The hypocretin neurons in the lateral hypothalamus (LH) have been implicated in wakefulness, but it is not clear which projection is responsible for the arousal. One possibility is that the LH neurons induce wakefulness by driving the basal forebrain (BF) wake-active neurons (Gerashchenko and Shiromani, Cellular & Molec Neurosci, 29: 41, 2004). Here we measure adenosine (AD) levels in the BF as a marker of arousal and test the LH-BF circuit in Sprague-Dawley rats with lesions of the LH induced by hypocretin-2-saporin. 64 days after lesions the rats were kept awake (gentle handling) for six hours (ZT 3-9) and microdialysis samples (5ul) were collected hourly for 9 hours (24h after probe stabilization). AD levels were assessed using HPLC. Hypocretin-saporin ablated 95% of the hypocretin neurons and reduced CSF hypocretin levels (-75% versus control). AD levels increased with 6h waking in saline control rats (n=9), consistent with previous studies in cats (Strecker et al., Behav Brain Res 115: 183, 2000) and rats (Murillo-Rodriguez et al., Neuroscience 123: 361, 2004). However, in rats with LH lesions (n=5) such an increase with waking did not occur. Sleep drive was measured by conducting a rodent version of a multiple sleep latency test (MSLT). In this test, conducted over 10h (from ZT2-ZT12) the rats were kept awake for 20min and then allowed 20min to sleep. The lesioned rats had more sleep during the 20min sleep periods indicating a higher sleep drive. These results suggest that in narcolepsy when the HCRT LH neurons die, there is a loss of stimulation of the wake-active BF neurons and the decline in this pathway may be the cause of the increased sleep attacks. Supported by VA Medical Research and NIH

Related Products: Orexin-B-SAP (Cat. #IT-20)