Download Single Neurons

Nick L. Theodorou
Department of Physics & Astronomy
[email protected]
Human Memory Retrieval
is predicted by Theta
Frequency Phase locking
of Single Neurons.
Based on Rutishauser et al. Nature 464 903- 7
Hypothesis
During memory retrieval a substantial
fraction of neurons produce spikes which
are phase-locked with the 3 – 8 Hz range
of the Local Field Potential.
Can an increase of phase-locked
spikes during learning predict an
increase in memory retrieval strength?
Method I
A memory test with two parts was
devised.
Learning: Patients were given a
set of 100 previously unseen images.
Recognition: Patients viewed a set
of 100 where 50 were previously
unseen and 50 were part of the
previous set. Patients decided on a
six point confidence scale whether
they had seen the image before or
not.
To segregate the data from the recognition
part of the test, the 50 images previously seen
were characterised into remembered or
forgotten; true positive or false negative.
Then
the neuronal activity was compared
between true positive and false
negative answers.
Method
II
To record the single neuronal activity
and the local field potential (LFP),
microwires were implanted into the
hippocampus and amygdale, part of a
technique known as Electrophysiology.
To compute results, data analysis was
done on: behaviour; spike sorting;
estimation of phase-locking; phasereset analysis; and the Spike-Field
Coherence.
If a difference between True Positive
and False Negative was found it was
verified using a control that had
randomly assigned labels TP or FN.
Motivations
The purpose of this investigation was to
investigate the formation and retrieval of
memory by recording the activity of a
population of single neurons. More specifically
this study chose to isolate brain oscillations in
the theta frequency range (3 – 8 Hz) as
synaptic plasticity is induced, and analyse the
synchronisation in terms of phase between the
local theta oscillation and the coordination of
‘spike’ timing. Spikes of individual neurons
timed against the local field potential (LFP) –
the ‘coordinated action-potential timing across
populations of neurons’. The LFP is the
favoured inducer of synaptic plasticity, and
synaptic plasticity is thought to underlie
memory formation.
The investigation is important because a fuller
understanding of memory formation would have
many medical applications, especially in
developing treatments for brain trauma or
epilepsy.
Results I
The behavioural results
of the test showed that
the Patients had a good
sense of the quality of
their memories as
confidence mapped well
on to performance.
The figure on the left shows
the receiver operating
characteristics were
asymmetrical which is
signature of recognition
memory dependent on the
Medial Temporal Lobe.
Right is a histogram of
the preferred phase of all
the neurons that were
phase-locked to an LFP
oscillation in the in the
theta range. This result
was the motivation for
the hypothesis. (n = 51 of 246, 21%)
Results II
The timing
between single
neuron spikes and
the ongoing theta
oscillation was
quantified by the Spike-Field Coherence.
If the SFC is larger, the more accurate it
can be said that a spike follows a
particular phase.
A striking difference was found:
The theta range Spike Field
Coherence for Remembered was
~50% higher than that for Forgotten.
Results III
Further data analysis was done using the
Spike-Triggered Average which is
constructed by averaging LFP segments of
± 400 ms centred on every spike. If a
logical relationship between the spike
timing and LFP exists, the resulting trace
will deviate from zero.
Strong oscillations in the theta range
were seen in each of the significantly
phase locked neurons.
Yet the power of the LFP when the spike
occurred did not distinguish between
Remembered and Forgotten results.
Conclusion
The results indicate further evidence
for the association of the theta range
with synaptic plasticity.
There are many factors such as novelty,
attention, and arousal influence the
effectiveness of memory formation.
However these results show that the
Spike Field Coherence may distinguish
between learning trials that were later
remembered and those that were
forgotten.
Further Reading:
Martin, S et al. Synaptic plasticity and memory: an
evaluation of the hypothesis. Annu. Rev. Neurosci.
23, 649–711 (2000).
Buzsa´ki, G. Theta oscillations in the hippocampus.
Neuron 33, 325–340 (2002).