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Book of abstracts - British Neuroscience Association

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68.01<br />

A comparison <strong>of</strong> carbachol and kainate-induced gamma and<br />

betaII oscillations in the rodent auditory cortex<br />

Roopun A K, Cunningham M O, Le Beau F E N, Traub R D,<br />

Whittington M A<br />

(1,2,3,5) School <strong>of</strong> Neurology, Neurobiology and Psychiatry, Medical<br />

School, Newcastle University, NE2 4HH. UK. (3) Neurology, SUNY<br />

Downstate, Med, Ctr., Brooklyn, NY, USA.<br />

High-frequency oscillatory activity at betaII (20-30Hz) and gamma (30-<br />

80Hz) frequencies is proposed to mediate cognitive processing in the<br />

cortex. Oscillatory activity is mediated by a variety <strong>of</strong> neuromodulators,<br />

including the cholinergic and glutamatergic system. Horizontal<br />

neocortical slices (450µm) containing deafferented auditory cortex<br />

were prepared from adult male Wistar rats and maintained at the<br />

interface between artificial cerebrospinal fluid and carbogen gas at<br />

34oC. Oscillatory activity was generated upon the application <strong>of</strong> the<br />

cholinergic agonist carbachol [25µM] or the glutamatergic agonist<br />

kainate [400nM]. Concurrent betaII and gamma oscillations were<br />

induced by carbachol (n=25), whereas only gamma oscillations were<br />

induced by kainate (n=25). Kainate-induced activity was resistant to<br />

the muscarinic-receptor blocker atropinµe [10µM] (n=6), and<br />

carbachol-induced oscillations was resistant to kainate-receptor<br />

antagonist UBP302 [10µM] (n=5), indicating two independently-driven<br />

networks producing a gamma oscillation. The similarities in gamma<br />

oscillations induced by kainate and carbachol were many-fold: the<br />

frequencies were similar, the peak power <strong>of</strong> oscillations were<br />

generated in superficial layers <strong>of</strong> the cortex, and all oscillations were<br />

abolished by carbenoxolone [100µM] (a gap-junction blocker),<br />

SYM2206 [20µM] (an AMPA-receptor antagonist) and bicuculline<br />

[2µM] (a GABAA-receptor antagonist) (n=6). Intracellular electrodes<br />

recorded gamma frequency firing from interneurons and gamma<br />

frequency IPSPs from pyramidal cells, suggesting an inhibitory-based<br />

oscillatory network. BetaII oscillations were only generated by<br />

carbachol, and may rely on intrinsically bursting (IB) cells interacting<br />

with an interneuronal network. This study indicates that cholinergic<br />

and glutamatergic systems operate independently in the auditory<br />

cortex, with the cholinergic drive exclusively producing a betaII<br />

oscillation.<br />

68.02<br />

Patterns <strong>of</strong> spontaneous activity in hippocampal cultures developing<br />

on multi electrode arrays: the influence <strong>of</strong> the NMDA receptor<br />

Charlesworth P, Eglen S J, Humphreys L, Morton A, Grant S G N<br />

Genes to Cognition Programme, The Wellcome Trust Sanger Institute,<br />

Hinxton, Cambridge CB10 1SA, Cambridge Computational Biology<br />

Institute, University <strong>of</strong> Cambridge<br />

We have used multi electrode arrays to record action potentials from<br />

developing embryonic hippocampal cultures and a suite <strong>of</strong> s<strong>of</strong>tware tools to<br />

analyse the resulting network activity. Action potentials are first observed at<br />

~ 4 days in vitro (DIV) and thereafter activity increases sigmoidally until a<br />

plateau at maturity (~20+ DIV) with a period <strong>of</strong> very rapid increase between<br />

~8 – 15 DIV. Concomitant with the rise in the number <strong>of</strong> spikes, a greater<br />

number <strong>of</strong> recording sites detect activity and also an entrainment <strong>of</strong> spikes<br />

into bursts is observed, such that by maturity most (~95+%) action<br />

potentials occur within bursts. Furthermore, these bursts show a<br />

progressively increasing degree <strong>of</strong> both temporal regularity and spatial<br />

correlation. Treating cultures with APV at DIV 6-7 (just prior to the rapid<br />

upsweep in network activity and synaptogensis) has a pr<strong>of</strong>ound effect on<br />

this developing spike pattern: burst patterns are less regular, both spatially<br />

and temporally, and many more non-bursting, individual, spikes occur. The<br />

overall number <strong>of</strong> spikes is however unaltered. We conclude that the<br />

NMDA receptor plays an important role in the development <strong>of</strong> spike pattern<br />

in culture, with implications for the transfer <strong>of</strong> information in neuronal<br />

networks. It is the aim <strong>of</strong> the Genes to Cognition programme<br />

(www.genes2cognition.org) to employ the MEA-culture platform and<br />

analytical methods developed here to phenotype mutant mice generated<br />

within the programme (see Kopanitsa et al, this meeting). We are also<br />

currently developing statistical methods for the automated analysis <strong>of</strong> these<br />

datasets as part <strong>of</strong> the CARMEN project.<br />

68.03<br />

Effects <strong>of</strong> DHEA administration on auditory evoked potentials<br />

Alhaj H A, McAllister-Williams R H<br />

Psychiatry, Leazes Wing, Royal Victoria Infirmary, Newcastle upon<br />

Tyne NE1 4LP<br />

Background: The adrenal steroid dehydroepiandrosterone (DHEA)<br />

has been shown to improve memory performance and modulate<br />

neural activity in rodents. Further, we have recently demonstrated<br />

beneficial effects <strong>of</strong> DHEA on long-term episodic memory performance<br />

in healthy humans. To further evaluate the effects <strong>of</strong> DHEA on<br />

attention and short-term memory in man, a study <strong>of</strong> auditory eventrelated<br />

potentials (ERPs) was conducted.<br />

Methods: Double-blind placebo-controlled crossover study in 24<br />

healthy men (aged 18 to 34). DHEA (300 mg/day) or placebo was<br />

administered for one week. Following each treatment period, subjects<br />

participated in an auditory oddball paradigm, during which subjects<br />

heard high (frequent) and low (rare) tones and were instructed to<br />

count the number <strong>of</strong> rare tones silently. Stimulus-locked ERPs were<br />

recorded from 29 scalp electrodes. The amplitude <strong>of</strong> the N1/P2 ERP<br />

components, and the latency and amplitude <strong>of</strong> the P3 component to<br />

rare tones, were calculated.<br />

Results: DHEA treatment led to a significant increase in the amplitude<br />

<strong>of</strong> the N1 component <strong>of</strong> ERPs recorded from posterior electrodes<br />

(p

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