organisation - the Instituto Gulbenkian de Ciência

NEURONAL
STRUCTURE
AND FUNCTION
Inbal Israely Research Fellow
PhD in Neuroscience, University of California, Los Angeles, 2004
Post-doctoral Associate, MIT, USA
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Research Fellow at the IGC since 2009
link to external website
We are interested in understanding how activity can lead to specific structural
changes in neurons which may be important for learning, and how such changes
affect connectivity within neural circuits. It is unknown how the diverse forms
of activity that a neuron receives are physically stored and regulated at the
level of individual spines, the sites of neuronal connections. Does long lasting
depression lead to structural changes at synapses? What types of structural
and electrophysiological modifications take place at spines following complex
patterns of naturally occurring activity? Several mental retardation disorders in
humans are characterised by abnormal spine morphology, and studying neurons
from animal models may further our understanding of the relationship between
structure and function. We aim to combine molecular and genetic tools with
imaging and electrophysiological methodologies, to determine how information
is physically stored in the brain.
GROUP MEMBERS
Yazmin Ramiro Cortes (Post-doc)
Anna Hobbiss (PhD Student)
Ali Ozgur Argunsah (PhD Student)
COLLABORATORS
Thomas McHugh (Riken Brain Science Institute, Japan)
Devrim Ünay (Bahcesehir University, Turkey)
FUNDING
Champalimaud Foundation (CF), Portugal
Bial Foundation, Portugal
DENDRITIC COMPARTMENTALISATION OF PROTEIN SYNTHESIS-DEPENDENT
SYNAPTIC PLASTICITY
We found that protein synthesis dependent stimulation of spines can facilitate
plasticity at neighbouring spines for up to an hour and over long distances (70
micra). Through 2-photon imaging and uncaging of glutamate at individual spines,
we aim to visualise structural changes that occur in response to protein synthesis
dependent forms of activity. We will examine how activity at multiple spines leads
to structural changes and changes in synaptic weights within a dendritic branch.
We aim to determine whether competition for proteins during synaptic plasticity
can shape the organization of inputs within a dendrite, leading to the physical
clustering of synapses. We also investigate whether the clustering of synapses
can be observed following the development of neural circuits, by examining the
endogenous distribution of spines within dendrites of the hippocampus.
We find that the stimulation of multiple spines closely together in time can
lead to competition for cellular resources, and that new proteins are required
for this process. These findings demonstrate that synaptic plasticity may be
biologically constrained, and provides a potential mechanism through which
synapses could be spatially clustered. We are examining the parameters over
which competition is regulated, in order to define the learning rules for protein
synthesis dependent plasticity.
STRUCTURAL CORRELATES OF SYNAPTIC DEPRESSION AT DENDRITIC SPINES
Synaptic potentiation leads to an enlargement of spine head volumes at individual
synapses, however the structural correlates of synaptic depression are
poorly understood. Long term depression can be initiated through a variety of
receptors, and it is unknown whether the structural correlates of this form of
plasticity apply generally to any decrease of synaptic weight, or whether there
are specific modifications depending on which signalling pathway is activated.
We aim to determine what are the structural correlates of synaptic depression
at dendritic spines. In particular, we are interested in exploring long lasting
forms of synaptic depression that depend on new protein synthesis. We will
determine what are the parameters which govern these changes following activity
at specific inputs. Additionally, we will probe whether new proteins serve
to constrain plasticity at multiple spines similarly to the case for long term
potentiation.
We have induced long lasting synaptic depression through the activation of
metabotropic glutamate receptors (mGluRs) in hippocampal organotypic slice
cultures. We have quantified the structural changes which correlate with this
form of plasticity through 2-photon imaging of subsets of spines for up to four
hours. Additionally, we recorded electrophysiological responses from these
cells in order to monitor the changes following synaptic plasticity.
INDUCING ACTIVITY AT SINGLE DENDRITIC SPINES TO STUDY STRUCTURAL DYNAMICS.
Using 2-photon microscopy in living brain slices together with photoactivation
of caged glutamate, we can examine how neurons physically store information at
synapses. We can vary the type of stimulation delivered at a given input to mimic
different forms of activity, and study what are the structural and functional correlates.
We also examine how a neuron integrates information arriving at multiple
synapses.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
75