January 05, 2005

Development of Synaptic Connections

Synapses. I like them. They are small and funky, like Christina. Unlike Christina, synapses permit signalling between an axon terminal and another neuron or cell type (for example a muscle fibre). When you decide you want to move your booty, for example, the signal passes down from your brain to your booty muscles via your spinal cord. Now, there is not one neuron that goes all the way from up there to down there. There are a few that form a chain. 'Synapses' are the gaps between two neurons. Or they can be thought of as the structure that includes the end of the first neuron, the gap, and the beginning of the second neuron. Or they are the end of the first neuron, the gap, and the bit of the muscle they are stimulating. Here is a picture of the brain-booty pathway.

Before we move on, have another look at this diagram. The first few synapses are connecting one neuron to another neuron, right? These are called CNS synapses. CNS means central nervous system. Again: neuron-to-neuron connections are CNS synapses. Now look at the last synapse. It connects a neuron to a booty muscle. Where a synapse is connects a neuron to a muscle, we call this a neuromuscular junction (or NMJ). Because it is a junction between a neuron and a muscle.

You're with me so far. I'm going to speed it up a little bit because I want to talk about the development of synaptic connections. Synapse formation takes place in a series of steps, and these steps are controlled by some crazy-but-impressive internal signalling between two nerves (for a CNS synapse), or between a nerve and a muscle (for a neuromuscular junction, NMJ). Once these connections have been formed, they are then refined by external sensory input. So basically, a bunch of connections are just splurged everywhere at first, and then, depending on how they are used, some die (or are killed off) and some remain. It sounds cruel, and let me be quite frank; it is. The nervous system is a dog-eat-dog-eat-synapse world. For the rest of this post, and in most literature you read, people will often only tell you about NMJ synapses and say: "er, this is probably true for CNS synapses, too." This is because it is much easier to study NMJ synapses than CNS synapses, so loads of research has already been done on it.

Look at the emphasis above: synapse formation controlled by internal signalling and refined by external sensory input. Those are the two stages in synaptic development and those are the two sections in this post. Let's start with section 1.

Section 1: Intrinsic Factors influencing Synaptic Development

Ok, so axons grow out from wherever they have originated from and head towards their target by a beautiful and still quite mysterious system of signalling methods. We are not concerned with how they get to how they get to where they are going, but are more concerned with how they make a synapse at their target. So how does the axon synapse onto the muscle at a NMJ?


It does it in only three steps!

(For legal reasons I must point out that although it does technically do it in only three steps, these three steps can fill most of a book. I will not fill most of a book. Scroll down and check if you are worried about being forced to fill most of a book.)

Here are the three steps if you are in a rush and need to quickly tell someone this. Maybe you are on a gameshow right now. Here is the answer but you should know this is a very stupid gameshow.

The three easy yet eyebrow-raising steps for synapse formation

1. The formation of some selective connections between the growing axon and its target (e.g. the muscle)

2. The shocking transformation of the tip of the axon (axonal growth cone) into a nerve terminal

3. The development of the amazing machinery in the target cell that will be able to the recognise signals given off by the axon.

Nice and vague. Science, eh? Who needs it?

The next post will go into these in more detail. My back hurts from typing so I am going to go to bed.

Posted at 9:36 pm | 1 comments

December 24, 2004

The fate of an ectodermal cell

What I learned this evening:

Is the default fate of an ectodermal cell to become a neuroepithelial cell? It seems to be, since neuroepithelial cells form when ectodermal cells avoid a variety of signals that induce non-neural fates, such as the bone morphogenic proteins (BMPs). Interesting. Have a look. And no, I didn't put that picture there for a specific reason except that I liked it.

Posted at 10:22 pm | 2 comments

December 21, 2004

In-depth: Reaching and Grasping


How do we decide how to pick up a glass of water? Many factors are involved in the decision:

- We must select the relevant target (the glass of water) amongst many stimuli (e.g. my lovely Mac)
- We must get information about the location of the target relative to our hand position
- We must determine the grip strength required to grasp and lift it, and open our grip to the appropriate size.

So; your brain asks 'what is it', 'where is it', and 'how shall I get it'.

Your senses, particularly sight, provide you with answers to these questions, and so the study of reaching and grasping can also be thought of as the study of how visual areas of the brain connect to the motor areas to result in the sensory guidance of movement.

In tackling the problem of the sensory guidance of movements, we need to think about the pathways that control these movements. As we mentioned at the start, what may seem to be a simple action (picking up the glass) may consist of several independent factors working together. Some neurones may be extracting visual data from the scene and sending this to a motor area for processing. Here, then, is the big question: we know all about visual areas, we know all about motor areas, but how are the two linked?

  • A quick history
  • The dorsal stream
  • This article is based largely on Mitchell Glickstein's excellent review paper .

    a quick history

    It was Munk in the 19th century who first identified the primary sensory and motor areas of the cerebral cortex. He noticed that injury to one side of the stritate (visual) cortex of the occipital lobe (called a unilateral lesion) caused the monkey to become blind in the visual field opposite to the one the lesion was in (known as hemianopia - "half-blindness").

    Henschen clarified further by stating that the left occipital lobe recieves input from the left half of each retina (and so the right half of the visual field), and vice versa. He also localised the upper bank of the calcarine fissures as the region that receives its input from the upper retina (and hence the lower visual field).

    Inouye constructed a more detailed map of what part of the visual cortex deals with what part of the visual field. The central visual fields seemed to be represented caudally (towards the back of the visual cortex) and furthermore seemed to occupy alot more cortical space than the peripheral visual field did. Holmes and Lister confirmed this in more detail in 1916.

    What about the motor cortex? It was later shown that if you weakly stimulated a bit of a dog's frontal cerebral cortex then you could cause movement of the face or of a limb on the contralateral (opposite) side of the body. Nice. If you cut out an area that elicited a particular limb movement, then that limb's movement would be impaired. Betz then descibed the pyramidal cells in layer V of cortex that we now associate with the motor area.

    So what of our big question, how do visual and motor areas link to produce sensory control of movement?

    Well, our main assumptions today are broadly similar to our assumptions in 1900, with, um, different terminology.

    The assumptions are:

  • a series of cortico-cortical fibres link sensory areas to motor areas ('cortico-cortical fibres' means 'a fibre linking one bit of the cortex to another bit of the cortex').
  • there are no direct connections from the primary visual cortex areas to the motor areas, instead, they are indirect, going through many links before reaching their motor target
  • the corpus callosum links the two hemispheres of the brain when required, for example if your visual cortex on one side has to be linked to the motor cortex of the other side of the brain
  • the dorsal stream

    There are thought to be two main classes that the extrastriate visual areas can be segregated into: a dorsal stream of information and a ventral stream. This was based on anatomical and behavioural studies. It was suggested that the dorsal stream was used more for the coding of an object's location, while the ventral stream was concerned with identification of the object.

    This theory was further reinforced by findings that these dorsal and ventral areas had very different projections: the dorsal, paretial areas were found to project heavily to the cerebellum via the pontine nuclei, while the ventral areas were found to show no such projection. It was suggested that the connections of the dorsal paretial areas to the cerebellum indicated that these areas might be important for the visual control of movement.

    To test this, they got a bunch of monkeys and lesioned their brains in different areas to see the results.

    The dorsal stream (shaded)
    The dorsal stream

    When they lesioned the dorsal stream, they found that monkeys were seriously impaired in their ability to guide their hands and wrists to pick up objects. Other lesioned areas had little or no effect. This was clear evidence that the first pathway between motor and visual areas was via the dorsal stream of extrastriate visual areas, as loss of these areas would severely limit ability to visually guide movement.

    Similarly, lesioning appropriate ventral stream areas will impair recognition of objects (or faces) but will not affect visually-guided coordination.

    So our next question is how this dorsal stream then goes on to control movement. To do this it has to somehow connect to the cortical and subcortical structures and interact with them, which will themselves control movement.

    Article to be completed later today... check back soon.



    This article is based on an excellent review by Mitchell Glickstein of UCL.


    Principles of Neural Science, p777: two pages, a basic introduction


    How are visual areas of the brain connected to motor areas for the sensory guidance of movement?
    Glickstein, Trends Neurosci. 2000, 23:12, 613-617

    Posted at 9:33 pm | 1 comments

    December 20, 2004

    Myelin repair gene found?

    MRI of spinal cord in MS patient

    Researchers working at Cambridge and Harvard Universities may have found a gene, Olig 1, that promotes the regeneration of myelin, the fatty covering of nerves that is lost during multiple sclerosis and which results in the debilitating symptoms of the disease.
    Researcher Dr Robin Franklin said: "This suggests that the Olig 1's function has been shaped by evolution to repair the brain in areas where the insulating layer of myelin has been depleted through disease."

    Read the article.

    Posted at 10:22 pm | 0 comments

    October 25, 2004

    Sainsbury's: Making Life Less Stressful

    Lord Sainsbury has opened a huge new research centre at the University of Bristol, looking into stress-related illnesses. The building is named after Nobel-prize winning scientist Dorothy Hodgkin.

    Researchers at the centre will focus specifically on how stress is perceived by the brain and its subsequent effects. Particular areas for study will be stress reactivity, stress and immune response, brain pathways activated by stress and stress induced coronary artery disease.

    Read the press release

    Posted at 12:10 am | 0 comments

    August 30, 2004

    Recommended books

    Here are a few Neuro-related books that I have found useful and/or interesting. I try to have read, or at least used a book before posting it. If you buy from Amazon UK via the link from here then I get a small cut which will help me through college! I own most of these books so if you want to ask me something more specific then go ahead.

    Core Textbooks (average weight > 2kg)

    Cognitive Neuroscience: The Biology of the Mind How does Gazzaniga find the time to write and edit so many books? Maybe he'll publish it in a paper one day. This text is concise and written in a very accessible style, and features many clinical case studies which are invaluable in aiding understanding. A recommended overview of the subject. coverPrinciples of Neural Science My most-used textbook. Is due for a new-edition, so misses some recent developments, but covers core topics step-by-step, and at the same time without patronising the reader.


    IQ and Human Intelligence A thorough and entertaining review of this frequently controversial topic. The book is openly opinionated, but will cover opposing theories in-depth before trashing their arguments.

    Popular Science

    The Emerging Mind The transcripts of an excellent set of lectures V.S. Ramachandran delivered for the BBC in 2003. Covers a wide variety of clinical and research topics in an accessible and entertaining style. Wow, I sound like the back of a book.
    See the BMJ review .
    Download the full lectures on MP3 here .
    Will be updating this list as I get more books!

    Posted at 2:47 pm | 0 comments

    August 29, 2004

    Mothers get angry

    Increased levels of a hormone have been shown to result in the loss of a mother's maternal aggression when protecting offspring. Mice injected with CRF (Corticotropin-Releasing Factor) were less aggressive towards potential threats to their offspring than those with a low or zero-dosage of the hormone. Other maternal behaviour was unaffected. Lead author Stephen Gammie said:

    "Low CRH levels appear to be a necessary part of maternal aggression. If you don't keep them low you won't see this fiercely protective behaviour. "You see this protective behaviour across the species. Mice do it, birds do it and so do humans. "It's a stretch from mice to humans but because this behaviour is so conserved between species it's not unreasonable to think this might be similar in humans."
    While this study will quickly be linked to papers that have investigated the relationship between high CRH and postnatal depression, groups have been quick to point out the danger in attributing the complex depression in humans to biochemical imbalances. Heather Welford from the National Childbirth Trust warns:
    "Postnatal depression, of all degrees of severity, is known to have many social and emotional aspects which are not accounted for in studies like this. "Maybe we can treat women with the right cocktail of drugs to reduce whatever excess is present. "But as an explanation of why some women suffer badly with postnatal depression, it doesn't get us very far."
    Read the BBC News article Read the abstract

    Posted at 1:08 am | 0 comments

    August 26, 2004

    Worm sex

    So we take a step closer to understanding our complex mate-seeking interactions thanks to the humble worm.

    Sexually mature males when left alone on a food source wandered off, presumably in search of a mate. When a potential mate was present on the food source, though, they remained.
    I'm not sure I'm comfortable with my mating habits being compared (admittedly very very loosely) with those of a worm. More importantly, this food/companionship model fails to explain why I don't wander off in search of a mate while I'm watching Late Edition at 3am with a box of Cheez-Its®. Where is the funding for that study?
    Read the news-release Read if you have a subscription to the Journal of Neuroscience.

    Posted at 11:44 pm | 1 comments

    August 25, 2004


    [This article is a stub. It will be expanded over the coming weeks!]
    Here is my list of the Neuro journals that I access regularly. Because not everyone has free access to these resources though college accounts, I will list the free-access journals first, then the paid-for journals. I will update this list slowly but surely... If you particularly like any other relevant journals, please tell me.

    Free-access journals

    Journal of Neuroscience / full text from May 1996 onwards neuroscience@nature.com / some free resources Entrez PubMed / includes over 15 million citations for biomedical articles back to the 1950's. If love is a website, this is it. Man, I am a geek.

    Paid-for journals

    Nature Neuroscience This is a very limited list of the journals that are out there. If you want a thorough, searchable database, Neuroguide.com is your best bet.

    Posted at 11:45 pm | 1 comments

    Think of a number

    Linguistic determinism is real? So suggests a newly published study which investigated a Brazilian tribe whose language does not define numbers above two. The tribe's language only has words for the numbers "one" and "two"; everything else is "many". When asked to tell the difference between a row of four objects and a row of five, they could not do so effectively.

    Experts agree that the startling result provides the strongest support yet for the controversial hypothesis that the language available to humans defines our thoughts.
    See the New Scientist article.

    Posted at 2:09 pm | 0 comments