Book of abstracts - British Neuroscience Association

35.01
Synchrony and sensory coding in the olivocerebellar pathway in
vivo
Schultz S R, Kitamura K, Hausser M
1 Dept of Bioengineering, Imperial College London, 2 Dept of
Neuroscience, Osaka University, 3 Wolfson Institute for Biomedical
Research, University College London
The climbing fibre pathway from the inferior olive to the cerebellum
has been hypothesized to provide information about non-anticipated
sensory signals for the modification of motor programmes. However,
the nature of the neural coding, and particularly the population coding,
of this sensory information is poorly understood. To investigate this,
we used two-photon imaging of calcium signals in multiple Purkinje
neurons loaded with membrane-permeant dye. Rats (P18-25) were
anaesthetized using urethane or ketamine/xylazine, and Purkinje cells
in the Crus IIa area of the cerebellum were bulk-loaded with AM-ester
calcium dye (Oregon Green BAPTA-1 AM) through a pipette inserted
into the molecular layer. As previously reported, calcium transients
triggered by spontaneous climbing fibre inputs were observed in the
Purkinje cell dendritic tree. These signals showed fine-scale spatial
structure, with synchronization between neighbouring neurons falling
off over hundreds of microns transversely. We investigated the role of
this synchronization in coding sensory information, by stimulating the
upper or lower lip with a brief airpuff. Using the two-photon
microscope, we were able to search in three dimensions for regions of
tissue in which sensory evoked calcium signals were to be found.
Sensory stimuli which evoked strong fluorescence responses
compared to baseline accentuated synchrony between nearby cells.
Periodic sensory stimuli were observed to result in the locking of
calcium signals to stimulus onset. These findings suggest that sensory
input modulates the fine structure of spatiotemporal patterns of
synchrony in the cerebellar cortex, perhaps by changing the dynamics
of oscillatory synchrony in the inferior olive.
36.01
Cholinergic neurons in human midbrain labelled with 125I Urotensin II
in post-mortem tissue in Progressive Supranuclear Palsy and normal
elderly
Piggott M A, Muelas M W, Burn D J
Dementia and Brain Ageing Group , Wolfson Research Centre , Newcastle
University Institute for Ageing and Health , Newcastle General Hospital ,
Westgate Road , Newcastle-upon-Tyne NE4 6BE
Progressive supranuclear palsy (PSP) is a disorder often misdiagnosed as
Parkinson’s disease, however patients do not respond well to levodopa.
Other clinical characteristics include postural instability resulting in frequent
falls, and symmetric signs with trunk more than limbs affected. These
features may relate to a greater pathological burden in nuclei that have
bilateral influence on the basal ganglia motor loop, including the
pedunculopontine nucleus (PPN). Degeneration of the PPN could also be
implicated in the absence of REM sleep in PSP. The PPN is severely
affected in PSP, with approximately 60% neuronal loss.
The PPN is located in the rostral midbrain and has connections with the
basal ganglia, thalamus, lower brainstem and spinal cord. Urotensin II
receptor transcripts and radioligand binding have been detected in
cholinergic neurones of rat midbrain, especially in PPN and the laterodorsal
tegmentum (LDTg) (Clark SD et al, 2001) where their presence may relate
to sensory-motor integration.
We have taken frozen sections from midbrain in PSP and normal elderly
controls at levels incorporating the PPN and LDTg. Sections have been
stained for acetylcholinesterase, with relative density of staining quantified.
Areas with strong staining include the PPN, LDTg, substantia nigra, raphe
nuclei, pontine nuclei, and cuneiform nucleus. Radioligand receptor
autoradiography has been carried out to visualise urotensin receptors (125I
urotensin II) showing binding localised to acetylcholinesterase-rich areas.
Specific binding was demonstrated by displacement with the antagonist
palosuran (gift from Actelion Pharmaceuticals Ltd), and unlabelled
urotensin. Urotensin II binding in PSP compared to control cases is
presented.
36.02
Computational Modelling of Neostriatal Neurons
Hoyland D, Wood R B, Overton P G, Gurney K
Department of Psychology, University of Sheffield, Sheffield, , United
Kingdom
Computational modelling at the biophysical level often encounters a
severe limitation in that the modelling enterprise is divorced from the
gathering of physiological data, and hence generic parameters, and
membrane behaviour gathered from the work of others, have to be
used. Here we present the results of an exercise to model certain
neuronal types from the neostriatum - medium spiny neurons (MSNs)
and fast spiking interneurons (FSNs) - using data gathered in parallel
with the modelling.
Brain slices (250-400µm) were prepared from rats at P14-19,
containing the neostriatum in coronal section. Electrophysiological
data were acquired under current clamp in the whole cell patch
configuration. The acquired data consisted of measurements of
voltage responses to short current pulses (to determine passive
membrane properties) and responses to longer duration subthreshold
and suprathreshold pulses (to activate voltage gated conductances).
Medium spiny neurons (N = 11) were identified by their hyperpolarised
membrane potential (-81.95mV ± 2.78) and long delay to first spike
(216.45ms ± 42.77) at rheobase. Fast spiking interneurons (N = 4)
were identified by high maximum firing frequency (typically around 75
Hz) and faster spike responses at threshold (132.50ms ± 58.10).
Passive membrane and voltage response data were used to drive a
parameter search algorithm developed previously by our group, which
refines models of the cell concerned until target voltage behaviour is
achieved. These models of MSNs and FSNs, and refinements that
take into account neuronal morphology, will be used to build large
scale striatal models for the investigation of striatal functionality.
36.03
How visual stimuli activate subthalamic neurones at short latency.
Graham J H, Coizet V, Overton P G, Redgrave P
Biology Dept., King College, Bristol, TN, USA, Dept. Psychology, University
of Sheffield, S10 2TP
The midbrain superior colliculus (SC) is one of a number of brainstem
sensorimotor structures that provides input to and receives output from the
basal ganglia (BG). Recently, the status of the subthalamic nucleus (STN)
as a major input station of the BG has been firmly established. Although the
STN is known to receive many afferents from the cerebral cortex,
comparatively little is known about inputs from subcortical sensorimotor
structures. We have recently described a pronounced projection to the STN
from the SC (Redgrave et al., 2005); however, the functional implications of
this connectivity are unknown. The purpose of the present
electrophysiological investigation was, therefore, to determine whether
short-latency visual signals are relayed to the STN from the visually
responsive SC. In the anaesthetised rat, cells in the intermediate and deep
layers of the SC, as well as cells in the STN, were found to be
unresponsive to a bright wholefield light flash. However, following a local
disinhibitory injection of the GABAA antagonist bicuculline into the SC, both
SC and STN neurons exhibited phasic, short latency responses to the
flash. These results demonstrate the SC is a major source of short latency
visual signals to the STN. This route could enable unexpected events to
interrupt ongoing behaviour. (Supported by BBSRC and Wellcome Trust)
Page 53/101 - 10/05/2013 - 11:11:03