Archive for the ‘Science’ Category

#SfN13: Day 2

Another poster from North Carolina caught my eye today. Zhenglin Gu and Jerrel Yakel, neuroscientists at Research Triangle Park in Raleigh, North Carolina kindly presented some compelling research about the medial septum to me. I know, I know, I posted research about the medial septum yesterday. But that little brain structure has a lot of secrets people are interested in!

Their study used a medial septum (MS)-hippocampus co-cultured preparation where both structures are removed from the brain and placed side by side for many days so that the MS can regrow connections to the hippocampus. They then looked at the cooperation between the MS and Schaffer collaterals (SC) in producing theta rhythms in the CA1 region of the hippocampus. Here's how it goes:

  • By just stimulating the SC with a stimulating electrode, no theta is evoked in CA1.
  • However, if you first stimulate the MS (they used channelrhodopsin with 10 ms pulses of light at 10 Hz for one second), and then stimulate the SC, they detected theta in CA1, measured with an extracellular recording electrode. They called this phenomenon theta "induction".
  • Then, after 3-5 times of this pairing between MS and SC inputs to CA1, something changes and simply stimulating the SC is sufficient to evoke theta. They called this theta "expression".

Induction of theta was blocked by the drugs atropine, MLA, and APV. Expression, on the other hand, was not blocked by atropine, MLA, or DHβE, but was blocked by APV. Clearly NMDA is important in this process.

Next, they looked at which type of receptors in CA1 neurons are necessary for this type of theta generation. They found that NMDA receptors on glutamatergic neurons weren't necessary, but that nicotinic acetylcholine receptors on GABAergic neurons were. Narrowing it down further, they discovered that somatostatin GABAergic neurons were necessary for theta induction, but parvalbumin GABAergic neurons were necessary for theta expression. They have yet to test the role of muscarinic acetylcholine receptors, but I think that's somewhere in the pipeline.

The next step they're going to work on is whole-cell recordings from single neurons in CA1 in order to understand their contributions to theta individually. One of the challenges in dealing with the medial septum and theta is that we have a growing body of observations that have yet to be linked together. I am hopeful that their research will combine with research from other labs to help bring the many pieces of the puzzle together and we will understand this important rhythm soon. See you tomorrow!

2013-11-10 22.19.12-1

#SfN13: Day 1

Today I had the treat of meeting Garrett Smith, a fellow North Carolinian, here from Davidson College in Davidson, NC (less than an hour from where I grew up! and where my sister-in-law currently works as an adjunct assistant biology professor). I planned on visiting his poster when I saw it dealt with medial septum (MS), a brain structure that I'm very interested in, and I was not disappointed.

Garrett was kind enough to guide me through his research: the MS provides excitatory cholinergic and inhibitory GABAergic inputs to the dentate gyrus (DG). In addition, a major input to the DG comes from the ipsilateral entorhinal cortex (EC) through the perforant path. There are also a small number of DG connections from the contralateral EC, but apparently not enough to cause depolarization to threshold in the DG (as measured by population spikes in the DG when the contralateral EC is stimulated).

All this changes when the ipsilateral EC is lesioned. Without the perforant path input, something signals the MS and the contralateral EC to form more synapses with the DG. The added input allows the contralateral EC, when stimulated, to provide inputs resulting in population spikes in the DG.

What Garrett's group found was that stimulating the MS shortly before stimulating the contralateral EC significantly increased the size of the population spike evoked from EC stimulation. This indicates that the MS could be involved in the recovery of learning and memory following an ipsilateral EC lesion in rodents by strengthening the contralateral EC input to the DG. What role exactly this plays in vivo is unknown, though it is compelling, as all these structures are involved in learning and memory.

The mechanism by which the MS achieves this potentiating effect is also unknown, but they plan on investigating it in future studies by studying how the DG responds to cholinergic and GABAergic inputs individually.

It was a good day, and I'm excited for tomorrow!

2013-11-09 23.12.46-1

Blogging at #SfN13

Good news! Between overeating and enjoying the sunny California weather, I will be writing daily posts from Saturday, November 9th, to Wednesday, November 13, as an official blogger for this year's annual Society for Neuroscience meeting! Specifically, my posts will focus on neural excitability and novel methods and technology development, though I may throw in some other things as well. I look forward to it! So stay tuned...

2013-11-05 16.42.51

Consciousness

The Scarecrow from The Wizard of OzThe cerebellum, the part of the brain that deals with motor learning, is a structure that makes up about 10% of the volume of the brain. It has many, many, tiny neurons in it, so much so that it actually contains more neurons than the rest of the brain. Interestingly, if the cerebellum is removed from someone's head, although they will have motor deficits, their personality and conscious experience of the world will remain unchanged. In contrast, even though the cerebrum has less neurons than the cerebellum, removal of the cerebrum will leave a person in a permanent, vegetative, and unconscious state. Something about the cerebrum that scientists haven't quite pinned down yet is responsible for conscious, subjective experience. I recently watched an excellent discussion among experts from different fields about the nature of consciousness, where they brought up this very point. I highly recommend the video, if only to see neuroscientist Christof Koch's fabulous shirt.

Although consciousness is difficult to define, much less explain, neuroscientists have made a lot of interesting progress in this area in recent years. It makes neuroscience an exciting field to be a part of, and is one of the things that drew me to neuroscience in the first place. What makes it so intriguing is its mystique--consciousness is one of the most scientifically intractable questions of which I know. It is easy enough to explain the neural mechanisms of something such as the tuning of an individual neuron in the visual cortex, but it is another thing entirely to explain what neural basis there is, if any, for the subjective experience of sight.

Neuroscience often teaches us to view the brain in terms of action potentials. Sodium atoms rush into the cell, potassium atoms rush out, causing a transient change in the local voltage. That's what the brain is: different types of atoms moving around in response to different forces. Harmonizing this deterministic, mechanical, soulless view of the brain with the idea of a subjective experience of consciousness is a difficult task. How can a large number of atoms moving around cause consciousness?

Christof Koch put it this way in an interview on NPR:

"So we know the brain is part of the physical universe, just like anything else. But brains - human brains, animal brains, baby brains - brains also exude this stuff, this feeling, like feelings of pain or pleasure, of artistic sensibility, of seeing red.

"And the big mystery has always been, how is it that a physical system that's described by the laws of physics, how can it give rise to conscious sensation? And can other physical systems such as a computer, can they also give rise to physical sensation? Is it something in the structure, is it something in the information, is it something in the complexity of it that gives rise to consciousness?"

He and another scientist, Giulio Tononi, are advocates of the idea that consciousness is a product of something called integrated information. As the name suggests, this theory borrows concepts from information theory and applies them to neuroscience, emphasizing that the integration of information across brain regions and modalities is critical to consciousness. They talk about this theory some in another video here.

Other scientists have recently developed alternative metrics for measuring consciousness. Traditionally, scientists observed electrical patterns recorded from EEG electrodes and then attempted to correlate them with behavioral manifestations of consciousness or unconsciousness, leading to some technologies such as the bispectral index, or BIS monitor used by many anesthesiologists to measure a patient's depth of anesthesia.

Recent studies using EEG have even found heightened signs of consciousness in rats for a short period of time immediately following death. This surprising result came when scientists found high levels of gamma rhythm synchronization between the front and back of the brain. Synchronous activity in the gamma frequency range is thought to be responsible for binding information from different brain regions together to make a coherent experience. However, it is important to remember that these studies do not measure consciousness directly, but rather measure electrical and behavioral correlates of consciousness.

Researchers in Italy and Giulio Tononi also came up with a new metric for measuring consciousness, called the perturbational complexity index, or PCI. Their metric also relies on EEG to measuring different large-scale electrical rhythms in the brain, and was developed by measuring these rhythms in people during a wide variety of different states of consciousness. Although they were able to distinguishing between different states of consciousness in test subjects using only their analysis of the subjects' EEG signals, many more people would need to be tested before this method became clinically relevant.

Yet other researchers have different theories about the nature of consciousness. Some postulate that quantum effects in the brain could explain consciousness. For instance, some have proposed that electrons in structural proteins called microtubules would be a possible candidate for information processing through quantum effects, allowing the brain to perform quantum computer-like calculations. There is even some evidence that microtubules are involved in anesthesia, which could lend support to this hypothesis, but many scientists feel this theory lacks substantial evidence.

Whatever the physical substrates of consciousness are, it will definitely be interesting to see where this field goes in the next few years. What do you think is the basis for consciousness? How should we measure it?