Lec2

HMB300H1S:The role of synapses in behaviour

January 13th, 2010 – Lecture 2

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Dr. Bill Ju105C Wetmore [email protected]@gmail.com

HMB300H1S - 2011 Semester - Dr. JU

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We will be studying behaviour atthe cellular and molecular levels with a strong emphasis on neuroanatomy

Two of the best studied behavioursare learning and memory

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Lecture Objectives - Review

• Review of the fundamentals• Brain, neurons and synapses• Synapse classification• Synaptic Plasticity

– Postsynaptic LTP and LTD– Trafficking of receptors? Movement of receptors?

• Specific case studies of synaptic plasticity• Synaptic Plasticity in Behaviour• Neurowiki groups – initial instructions

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• Behaviour (learning, memory, emotions, cognitive functions) exists because we have a brain

• These behaviours arise specifically because of the specific electrochemical connections between the neurons (~100 billion in the brain; ~20 billion of these in the frontal cortex)

• The smallest definable unit in these connection is the synapse

• Modifying synapses therefore should modify behaviour (or modifying enough of these)

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Core FundamentalsH

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• Frontal lobe is vital for many different behaviours:– Executive brain– Problem-solving– Planning tasks– Movement– Emotions and emotional

responses– All sensory systems in the

brain send information to this region (but …)

– Hemispheric differences

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A colourful brain

http://serendip.brynmawr.edu/bb/kinser/Structure1.html

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Where we’re heading

This area of the brain is believed to be particularly important

• easily distracted/attention deficits

• disturbances in memory • defects in “time sense”• less critical of oneself • difficulty with unfamiliar

analogies (I don’t get it!)• impulsivity/gambling• emotional disturbances • apathy, withdrawal, euphoria,

irritability, and obscene language.

http://www.humboldt.edu/~morgan/images/fro3_s05.jpg

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• Lesion studies still best method to study the function of specific brain areas

• Fronto-temporal dementia

• Phineas Gage – old news

• MGS: July 1999, Neurocase (Dimitrov et al)

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http://pathology.mc.duke.edu/neuropath/CNSlecture4/pickgross.jpg

In the next few lecturesH

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Neurons are useless

• Neurons form synapses and require these in order to pass on information to the next neuron

• Important concept of interconnectivity especially within the frontal cortex

• This is how neurons communicate and transfer/encode information

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What’s the evidence for synapses?

• Originally related more with neurodevelopment – increased numbers of synapses

• Other aspects of neurodevelopment have also shaped our understanding of synapses as being key players in behaviour and changes in behaviour

• Which developmental disorders, involving behaviours would you investigate?

• What other disorders would you investigate?

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Synapses - Classifications

Chemical Synapses• Allow for many

different electrophysiological processes – such as summation,

pre-synaptic effects, one-way propogation of information (i.e. electrical impulses)

• Pre-/Post- elements

Electrical Synapses• Significantly fewer in

the brain• Allow rapid, bi-

directional transfer of ions/electrical impulses from neuron to neuron

• Connexons formed between neurons

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Synapses in the Brain - Chemical

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Changing Chemical Synapses

• Are new roles being defined for synapses and the proteins within them?

• New terms such as extrasynaptic and synaptic relocalization of receptors and subunits

• Still many controversies• NR2A versus NR2B – scaffolding proteins

associated with these?• Inhibitory synapses as well? a5 subunits?

HMB300H1S - 2011 Semester - Dr. JU 12

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• Are new roles being defined for synapses and the proteins within them?

• New terms such as extrasynaptic and synaptic relocalization of receptors and subunits

• Still many controversies• NR2A versus NR2B – scaffolding proteins

associated with these?• Inhibitory synapses as well? a5 subunits?


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Synapses in the Brain - ElectricalH

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Synapses are modifiable

• The vast majority of neurons communicate with their neighbours via chemical synapses

• This form of communication can be strengthened (i.e. for the same presynaptic stimulus, a stronger synapse will respond with a greater depolarization) - LTP

• Synapses can also be weakened – LTD

Not the case that LTP strengthens and LTD weakens. Not a liner relationship

• Many synapses that can be modified have been used to study learning and memory – the vast majority of these are excitatory synapses

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Synaptic Plasticity

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• Synaptic plasticity (strengthening or weakening) involves modifying a neural circuit

• May involve neurons, structural plasticity as well as LTP/LTD of specific synapses

• Ultimately, both neuroscientists and cognitive neuroscientists believe that changes in the synaptic strength alters behaviour (learning, memory, drug addiction, others?)H

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• Electrical model

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Memorized this yet?H

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Different Theories

http://www.nature.com/nrn/journal/v10/n9/box/nrn2699_BX2.html

More spines?

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• Appears to be experience or pathway dependent in the models – a good thing!

• Appears to involve the trafficking specifically of AMPA type receptors

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Is this model correct?H

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• Remember we have been primarily examining the hippocampus (a structure strongly implicated in learning and memory)

• Can we increase learning and memory by increasing AMPA receptor trafficking?

• Drugs that have been shown to have a positive cognitive enhancing effect (Adderall) do not seem to work on this pathway

• Does this work in other areas of the brain?• If so, could we alter behaviours associated with

those areas/neurons?21

Using this to your advantageH

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• A lot of indirect evidence to show that there are post-synaptic changes in neurons following electrical stimulation

• Direct proof? Very little but neuroscientists have been trying to link these cellular and molecular mechanisms directly to behaviour (i.e. memory)

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Lack of a smoking gunH

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Why is this so difficult to link?

1. Difficult because in order to show this in an intact animal need to train – variation and as such LTP difficult to detect

2. It is not every single synapse within the hippocampus that gets altered so it would be difficult to detect

3. There is increasing evidence that in addition to LTP, LTD is equally important so that maybe this is not the only mechanism?

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• First to show that LTP does actually occur as learning occurs

• How did he do this?• Needed a good model

for learning and some sophisticated techniques for analysis

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Specific Case Study 1 - SuccessH

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LTP and Learning at Picower

• Used a model of animal learning – inhibitory avoidance (passive avoidance)

• There are 2 chambers – an upper lighted chamber and a darker one

• Receive a shock when they step down• They must learn to avoid this task

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Cool experiment but…H

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• LTP probably influences behaviour in the form of memory and learning

• But I happen to remember things for longer periods of time - so what is really happening?

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Long-term or short-term effects?H

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• Remember (hopefully) from earlier in this class that we have 2 different classes of synapses

• We have been dealing with chemical synapses up til now, but are their counterparts are also modifiable?

• If they act like other synapses and synapses underlie neuronal function, changing synaptic strength should alter behaviour

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Other synapses?H

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• Importance of these synapses – excellent for synchronization (i.e. rhythms)

• Measured electrical activity from rat thalamoreticular neurons

• Landisman and Connors (2005) found that either with direct electrical stimulation or stimulating an electrically coupled cell, you activate mGluRs

• Results in a long-lasting depression in the electrical coupling at these junctions

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LTM of electrical synapsesH

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• The sets of neurons used were inhibitory• By reducing the junctional coupling of these

neurons, you are increasing activity of their downstream target neurons (thalamic relay neurons)

• These neurons may be potentially important for alertness and wakefulness during various sensory stimuli

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Is there a behavioral significance?H

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• Things that you should know from this lecture:• Principles and cellular mechanisms underlying

synaptic plasticity• How synaptic plasticity alters behaviour – which

molecules in theory could enhance memory retention?

• Neurowiki planning - initial

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Lecture Summary + class activityH

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