Book of abstracts - British Neuroscience Association

13.06
Contribution of synaptic conductance to the action potential
waveform at the calyx of Held/MNTB synapse
Postlethwaite M 1,2, Johnston J 1,2, Forsythe I D 2
1 Department of Cell Physiology and Pharmacology,, 2 MRC
Toxicology Unit,, University of Leicester,, University Road,, Leicester,,
LE1 9HN
The calyx of Held projects onto neurones of the medial nucleus of
the trapezoid body (MNTB). This pathway is involved in brainstem
auditory processing for sound localisation. The calyx synapse has a
very strong safety factor, with an EPSC being 31 times the current
required for action potential (AP) generation so that the postsynaptic
cell always fires an AP.
Traditionally, direct injection of square current pulses are used to
trigger AP firing and elucidate the roles of voltage-gated channels.
However we show that APs generated by such stimuli are distinctly
different from those triggered by orthodromic synaptic currents.
Physiological synaptic stimulation (at 37°C) generates an AP with an
apparent after-depolarisation which is never observed when using
square current pulse injections. This after-depolarisation was
unaffected by NMDAR antagonists. We demonstrate that the afterdepolarisation
is the result of a slower component of the AMPAR
mediated EPSC. Furthermore the amplitudes of orthodromicallyinduced
APs were smaller than those evoked by current injection, and
rarely overshot 0mV. This finding is explained by shunting of the AP
by the EPSC.
Our findings demonstrate that synaptic conductances can influence
the AP waveform, and highlight the importance of considering the
actual physiological stimuli in studying AP initiation.
13.07
The small heat shock protein family: Physiological expression in the
mouse cns.
Quraishe S, Wyttenbach A, Holden-Dye L, O`Connor V
Neuroscience Research Group, School of Biological Sciences, University of
Southampton, UK, SO16 7PX
The small heat shock protein (sHsp) family comprises 10 members of low
molecular weight (15-30kDa). These proteins contain a characteristic C-
terminal α-crystallin domain that supports their function as molecular
chaperone. They are thought to play a role in protein misfolding diseases,
such as neurodegenerative disorders, cataract, and desmin related
myopathy.
The 10 members are believed to have a unique expression profile in
different tissues. Heart and muscle are the two tissues in which up to seven
sHsps are expressed. Little is known about the physiological role of the
sHsps in the CNS. We have analyzed expression of all 10 family members
in various tissues including the brain. We have confirmed the tissue specific
expression of the sHsps in the various tissues of the body by RT-PCR and
have found 7 to be expressed in the brain, 3 of which (B3, B7 and B9) have
previously not been reported in the brain. In-situ hybridization using naïve
animals evidenced a white matter specific expression pattern for HspB5.
HspB1 and HspB8 are expressed in the spinal cord. HspB8 is also
expressed in the cerebellum. Antibody characterization has confirmed
protein expression of HspB1, HspB5, HspB6, HspB8 and potentially HspB9
in the brain, highlighting a potential role for these sHsps as components of
the chaperone machinery in the CNS.
Sponsored by the MRC and BBSRC
13.08
GABAA receptor beta3 subunit N265M mutation introduces
heterogeneity in GABA sensitivity into cultured posterior
hypothalamic neurons
Sergeeva O, Hatt H, Haas H
Institute of Neurophysiology, Heinrich-Heine-University, Duesseldorf
and Department of Cell Biology, Ruhr University Bochum, Germany
The histaminergic tuberomamillary nucleus in the posterior
hypothalamus controls arousal and attention. Acutely isolated neurons
from this region show a remarkable range of GABA sensitivities
(EC50s 2 to 100 µM). This heterogeneity was not found in primary
cultures of posterior hypothalamus indicating that it is not genetically
programmed. Also co-cultures of dissociated posterior hypothalamus
with explants either from cortex or lateral hypothalamus did not
develop such heterogeneity. As the GABAAR beta3-subunit is
expressed transiently during embryogenesis at a high level in many
brain structures it may be involved in shaping the GABAAR. To
discriminate between neurons expressing only the beta3-subunit and
neurons expressing a mixture of beta-subunits we took advantage of
the mutation b3N265M (Jurd et al. 2003) which introduces propofolresistance
to the GABAAR. In mainly beta3-expressing cells propofol
enhanced GABA responses by