Beyond Neurotransmission Journal Club

Meeting Calendar

Next meeting:

• 4pm Fri 3/4/09 @ Informatics forum room 3.02
• Why have dendrites?
  • Why have dendrites, Bartlett Mel (2006), Dendrites.

In the last decade computational modelling of neurons has progressed from simple connectionist models to ever more detailed models based on biological data. It is now quite common to see complex model neurons with ion channel distributions derived from experimental data, but it is still unusual to see as much care being put in to reconstuct the morphology of the cell.

Is this a reasonable approach to take, or is there to much focus on ion channel electrophysiology at the expense of understanding the effect of neuronal morphology? Should we allocate more of our computational resources to understanding the role of the dendrites rather the precise mechanisms of spike generation?

In this weeks journal club we will review a book chapter that offers a refreshing perspective on the importance of dendrites.

Cian will introduce the chapter.

Past meetings:

• 4pm Fri 20/3/09 @ Informatics forum room 3.02
• The role of astrocytes in generating the BOLD signal
  • Tuned Responses of Astrocytes and Their Influence on Hemodynamic Signals in the Visual Cortex, Schummers et al (2008), Science.
  • Locus Coeruleus alpha-Adrenergic-Mediated Activation of Cortical Astrocytes In Vivo, Bekar et al (2008), Cerebral cortex.

Recent advances calcium imaging appear to have solved the riddle of how the BOLD signal in fMRI relates to neural activity. Results from a 2008 paper by Sur et al indicate that the BOLD signal is an indirect measure of astrocyte activation. Surprisingly, in the same study they report that astrocytes in the visual cortex are more sharply tuned to spatial orientation and frequency than neurons in the visual cortex.

What is happening here? If we previously assumed that fMRI signals indicate the activation of internal mental states, does this now force us to conclude that astrocytes are involved in the process of representing our mental states, of seeing?.... Or is the activation of astrocytes merely a result of them clearing up neurotransmitter after the real representational work has been done by neurons?

• 4pm Fri 6/3/09 @ Informatics forum room 4.02
• The practical difficulties in relating synaptic plasticity protocols to memory
  • Cytokine Responses to LTP Induction in the Rat Hippocampus: A Comparison of In Vitro and In Vivo Techniques, Jankowsky et al (2000), Learning and Memory.
  • Long-lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment, Artola et al (2006), European Journal of Neuroscience.

Today the most common paradigm in neuroscience for studying memory is synaptic plasticity. Experiments intended to measure synaptic plasticity often assume that changes in synaptic efficacy following a tetanic stimuli from implanted electrodes relate to the physiological processes that underly memory.

Is this a reasonable assumption to make, or does the act of preparing brain slices, implanting electrodes, or electrically stimulating neurons invoke cellular processes that are not related to the changes that happen under physiological conditions? Do changes to the animal's environment or social status prior the experiment have a greater effect than the experimental protocol? Is it possible to measure synapses without changing them?

Our first paper addresses this question by looking at the effect of measuring synaptic plasticity on the expression of plasticity-modulating cytokines.

While our second paper looks at the effect of longer term stressors and behavioural changes on the outcome of plasticity measurements taken many months later.

* 4pm Fri 20/2/09 @ Informatics forum room 3.02

• Neural Darwinism : Evolution in the brain
  • Artificial Evolution in the physical world, Thompson (1997), Evolutionary Robotics.

If the brain is an artifact produced by evolution should we expect to be able to decompose it into component parts which can be understood in isolation? Or conversely, in computational neuroscience, should we be attempting to build models of the brain and behaviour by combining non-linear mechanisms into larger computational models, and expect this to compare to how the brain functions?

Our reading this week looks at a study which has examined these questions in the context of robotics.

Hugh Pastoll will give a brief introduction to the paper.

You may find it helpful to read the article in the context of Neural Darwinism. You can find a short summary of the theory at http://www.mindcreators.com/NeuralDarwinism.htm

• 4.30pm Thu 5/2/09 @ Informatics forum room 3.02
• The biological basis of decision making and cognitive control : in the immune, endocrine, or central nervous system?
  • Modulating the modulators: parasites, neuromodulators and host behavioral change, Adamo (2002), Brain, Behaviour and Evolution.

It is usually assumed that the biological basis of cognitive control is in the neural activity of the prefrontal cortex. Historically, this line of thinking comes from neuropsychology, where patients with lesions to these areas display profound disabilities in decision making and executive function.

However, evolution appears to be telling us something quite different. Organisms such as parasites, which ought to have evolved the most simple mechanisms for controlling their hosts, exert their control in quite a different way. For a graphic example of parasitic manipulation see Bizarre Ant Fungus Makes Heads Explode!.

How does the fungus control the ant, and what implications does this have for our models of decision making and cogitive control? Are decisions made in the immune, endocrine, or central nervous system? Do we think in our bodies or our brains?

The readings for this discussion will be quite eclectic, so we'll start with a short presentation to kick-off the debate

• 2pm Thu 13/11/08 @ Informatics forum room 3.02
  • Dendritic transmitter release: a comparison of two model systems., F Bergquist, M Ludwig (2008)
  • Emergent Synchronous Bursting of Oxytocin Neuronal Network, Enrico Rossoni, Jianfeng Feng, Brunello Tirozzi, David Brown, Gareth Leng, Françoise Moos., PLoS Comput Biol (2008)

This week we will look at two papers that describe phenomena that fall outside the classical view of neurotransmission. The first is a review of neural systems that communicate via transmitter release from the dendrites, while the second paper offers a model of how dendritic neuromodulation may be responsible for the bursting of oxytocin neurons in the milk let-down reflex. Duncan MacGregor may also give a brief introduction to his research doing computational modelling in neuroendocrinology.

• 2pm Thu 30/10/08 @ Informatics forum room 3.02
  • Introduction, Beyond Neurotransmission, Paul Katz (1999)
  • The Neuron Doctrine, Redux, T. H. Bullock et al., Science (2005)

Introduction

Rather than attempt to explain the rationale for this journal club myself, I'll leave you with the words of some more eloquent writers:

"A basic principle of nervous system operation, arising out of the neuron doctrine itself, is that neurons communicate 'information' to one another. This information is passed from neuron to neuron through the nervous system, allowing animals to sense their environment, move through it, learn from it, and act on it. The information itself takes many forms and it is increasingly evident that there are a great many ways that it is communicated between neurons. Recognition of the variety of mechanisms used by the nervous system for communication of information is necessary before we can understand the cellular basis for complex types of behaviour. Commonly, chemical communication between neurons is thought to be fast (millisecond time scale), point-to-point (neuron-to-neuron), and simple (either excitatory or inhibitory). These are hallmarks of what we generally call neurotransmission. Neurotransmission is almost universally acepted as the primary means of communication between neurons. Thus, most discussions of information flow and circuit organisation in the nervous system include only neurotransmission. Yet there are many instances where interneuronal communication does not display all of these traits. In fact, the vast majority of substances synthesised and released by neurons have some effects that would not fit this characterisation of neurotransmission. Thus, to fully comprehend how information is conveyed in the brain, we must look beyond simple neurotransmission and into other modes of communication."

Paul Katz, Beyond Neurotransmission (1999)

"After a century, neuroscientists are rethinking the Neuron Doctrine, the fundamental principle of neuroscience. This proposition, developed primarily by the great Spanish anatomist and Nobel laureate Santiago Ramòn y Cajal, holds that a neuron is an anatomically and functionally distinct cellular unit that arises through differentiation of a precursor neuroblast cell. In principle, part of this tenet has held up, but technology and research have extended our knowledge far beyond this simple description. What has evolved is a modern view of the neuron that allows a more broad and intricate perspective of how information is processed in the nervous system. One hundred years since its inception, an examination of the Doctrine indicates that it no longer encompasses important aspects of neuron function. If we are to understand complex, higher level neuronal processes, such as brain function, we need to explore beyond the limits of the Neuron Doctrine."

T. H. Bullock et al., The Neuron Doctrine, Redux, Science (2005)

"Consider, for example, if calcium imaging had been invented before micro-electrode recording. Researchers might then believe that calcium is the key signal for neuronal communication. The rise and fall of Ca2+ in the cytoplasm has time and length constants just as general ionic charges do. Thus it would appear to researchers in this altered history that changes in Ca2+ concentrations were the primary mode of communication. When microelectrodes are later invented, researchers might think that the membrane potential of a cell is just another means of elevating Ca2+, not the primary mode of communication as is now believed."

Paul Katz, Beyond Neurotransmission (1999)

Summary

The intention of the Beyond Neurotransmission Journal Club is to provide a forum for discussing papers which fall outside of the neuron doctrine, or papers which encourage us to look for alternate ways of understanding the workings of the nervous system. Topics will include, but are not restricted to:

• Neuromodulation
• non-synaptic communication
• non-synaptic plasticity
• Neuroendocrinology
• Reinforcement Learning
• Neural synchrony and oscillations
• Psychoneuroimmunulogy (phew!)
• Neural Darwinism
• Philosophy of mind

the aim is not decide upon which approaches are right and wrong, but to encourage a proliferation of views and offer an opportunity for finding a new perspective on old problems. We hope you enjoy the debate....

Future papers & paper suggestions

We keep a list of potentially interesting papers on our Beyond Neurotransmission citeulike group. You are welcome to add any papers you think might be of interest.

Group contact

Robert Kyle