Wednesday, 11 April 2007

Blimey!

Interview on USC hippocampal prosthesis

Interview with Ted Berger of USC on their hippocampal prosthetic project in Popular Science magazine

To summarize the most interesting info from the interview:

Berger’s team is trying to make a hippocampal prosthesis (a chip that could be implanted in the hippocampus and help people with damaged hippocampuses). (we’ve mentioned Berger’s team’s efforts before).

He admits that he doesn’t understand how the hippocampus functions in memory, but argues that you may be able to make a prosthesis without this understanding: “A repairman doesn’t need to understand music to fix your broken CD player.”

The first crucial test will be done later this year by Sam Deadwyler at Wake Forest. He will implant the chips in rats, deactivate their hippocampuses with drugs, and see if the prosthetic helps.

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Interesting

Enabling Neural Engineering Ought To Be The Measure Of Neuroscience

The field of neuroscience naturally focuses its inquiry into neurons. This approach to understanding the brain by studying its parts has been thought to have a greater potential than that of psychology to understand how the brain works, a comment made by no less than Daniel L. Schacter, chair of Harvard’s Department of Psychology, in his book, The Seven Sins of Memory.

However promising the field has been thus far, even the most accomplished neuroscientists will admit that we still do not understand how the brain really works. I would submit that the current reductionist nature of neuroscience has shed much light on the dynamics of how neurons work, but has to a far lesser degree shed light on how neurons process information. The difference between these two lines of inquiry is important for making progress in understanding how the brain works.

A computer, at its core, processes information through the physics of transistors, which are essentially switches that are either on or off. What makes transistors such a powerful foundation for modern computing is that they are controlled by electrical signals, which means that transistors can be controlled by other transistors and therefore structured into useful systems. Understanding the
physics of transistors, how quickly they can switch from on to off, how their material composition affects their ability to switch, is crucial for building a microchip. However, this level of understanding is not sufficient to build a microchip. For that, one needs to understand how to structure transistors in such a way to produce digital computation.

Single transistors turn on and off. As a medium for constructing computer architectures, they are relatively straightforward to combine into complex circuits that perform useful functions of logic. Single neurons, quite a bit more complicated, have a vast repertoire of behavior that, among other things, involves integrating signals from multiple sources and sending signals to multiple recipients. It is not at all straightforward to construct explanations of how neurons combine into complex circuits to perform useful behavioral functions. Yet, this is the kind of explanation that neuroscience ultimately must seek in order to fulfill the promise of its potential to unlock the secrets of the brain.

Keeping in mind that computers are different that brains in many important ways, in some sense, we are still at the level of understanding the dynamics of the transistors in neuroscience. Cellular neuroscience, as found in journals such as Neuron, has concerned itself with the dynamics of neurons, rather than their role in processing information. This may seems like a bold statement to some; after all, decades of research has been conducted on sensory systems such as vision, and many aspects of the visual pathway are understood. Furthermore, lesion studies have been demonstrating that certain groups of neurons have certain functions throughout the last hundred years. However, despite the current push to apply information theory into the study of sensory systems, even the most cutting edge work in the field of neuroscience is still only just beginning to incorporate the understanding of what single neurons do with a rigorous account of how they carry out the functions they perform.

Other flavors of neuroscience, such as systems neuroscience and cognitive neuroscience have made inroads towards this goal. For example, excellent progress has been made in understanding the olfactory system of the locust. Here is a system where we understand the inputs, we understand the physiology of the neurons in between, and we have ways of analyzing the dynamics of the system that allow us to predict future behavior. And yet, the difficulty of generalizing these findings to more complex neuronal systems looms large as an obstacle to progress. Some of the best accounts of the activity of neurons in the pre-frontal cortex of monkeys still only provide a descriptive model of the data that fits the observations but does not provide a complete explanation for how the system actually carries out the function that is being modeled. This is the rule, rather than the exception in neuroscience.

One of the key difficulties is that processing information does not happen in single transistors by themselves, nor does it happen in single neurons by themselves. Both systems require the coordinated spatiotemporal organization of an complex system. Engineers over the past 60 years have constructed patterns that help organize transistors into useful components that process information. The most basic functions are those of basic logic, AND, OR, and NOT. Using these tools, arithmetic can be carried out to add, subtract, divide, and multiply numbers encoded in ones and zeros. From there, computer programs can be constructed in a straightforward manner and provide the foundation upon which more complex computer programs can be constructed. We have no equivalent explanation for the functions that assemblies of neurons carry out. We know that neurons excite or inhibit one another, and that the influence between two neurons can change. But neuroscience does not yet have the ability to recombine biologically faithful model neurons into novel circuits to perform novel functions. This indicates that the field lacks principles, or at the very least a sufficient set of well-understood patterns, which explain how neurons are organized together to enable an animal to behave in an appropriate manner in its environment.

In summary, while understanding neuronal dynamics is necessary to understanding the brain, it is not sufficient. I would posit that we must understand how the brain processes information in order to understand it as a whole. A prerequisite to understanding how the brain processes information is to describe principles of neural information processing, which a) explain how neurons perform functions collectively, b) help us to explain the functions of those parts of the brain where they are still unknown, and c) are rigorous enough to enable the design of circuits of neurons (model neurons, or eventually real physical neurons) that perform known and novel functions–true neural engineering.

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Grower tried - medical use was epilepsy

Appeals heard on both medical and non-medical marijuana.


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Appeals heard on both medical and non-medical marijuana.

Can HIV AIDS Policy Law Newsl. 2000 Spring-Summer;5(2-3):8-9, 9

Authors: Elliott R

In October 1999, the Ontario Court of Appeal heard an appeal in the case of R v Parker. Terry Parker was charged in 1996, after a police raid on his home in which the marijuana plants he was growing to ensure a supply in order to control his epileptic seizures were confiscated.

PMID: 11833209 [PubMed - indexed for MEDLINE]

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Bettina and Ca2+ imaging with CBD

Interactions of cannabidiol with endocannabinoid signalling in hippocampal tissue.


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Interactions of cannabidiol with endocannabinoid signalling in hippocampal tissue.

Eur J Neurosci. 2007 Apr 10;

Authors: Ryan D, Drysdale AJ, Pertwee RG, Platt B

The phytocannabinoid cannabidiol (CBD) possesses no psychotropic activity amid potentially beneficial therapeutic applications. We here characterized interactions between CBD (1 microm) and the endocannabinoid system in cultured rat hippocampal cells. The CBD-induced Ca(2+) rise observed in neurons and glia was markedly reduced in the presence of the endogenous cannabinoid anandamide in neurons, with no alteration seen in glia. Neuronal CBD responses were even more reduced in the presence of the more abundant endocannabinoid 2-arachidonyl glycerol, this action was maintained in the presence of the CB(1) receptor antagonist AM281 (100 nm). Neuronal CBD responses were also reduced by pre-exposure to glutamate, expected to increase endocannabinoid levels by increasing in [Ca(2+)](i). Application of AM281 at 1 microm elevated CBD-induced Ca(2+) responses in both cell types, further confirming our finding that endocannabinoid-mediated signalling is negatively coupled to the action of CBD. However, upregulation of endogenous levels of endocannabinoids via inhibition of endocannabinoid hydrolysis (with URB597 and MAFP) could not be achieved under resting conditions. Because Delta(9)-tetrahydrocannabinol did not mimic the endocannabinoid actions, and pertussis toxin treatment had no effect on CBD responses, we propose that the effects of AM281 were mediated via a constitutively active signalling pathway independent of CB(1) signalling. Instead, signalling via G(q/11) and phospholipase C appears to be negatively coupled to CBD-induced Ca(2+) responses, as the inhibitor U73122 enhanced CBD responses. Our data highlight the interaction between exogenous and endogenous cannabinoid signalling, and provide evidence for the presence of an additional pharmacological target, sensitive to endocannabinoids and to AM281.

PMID: 17419758 [PubMed - as supplied by publisher]

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CB1 and glutamatergic transmission

CB(1) cannabinoid receptors inhibit the glutamatergic component of KCl-evoked excitation of locus coeruleus neurons in rat brain slices.

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CB(1) cannabinoid receptors inhibit the glutamatergic component of KCl-evoked excitation of locus coeruleus neurons in rat brain slices.

Neuropharmacology. 2007 Feb;52(2):617-25

Authors: Mendiguren A, Pineda J

CB(1) cannabinoid receptors located at presynaptic sites suppress synaptic transmission in the rat brain. The aim of this work was to examine by single-unit extracellular techniques the effect of the synthetic cannabinoid receptor agonist WIN 55212-2 on KCl-evoked excitation of locus coeruleus neurons in rat brain slices. Short applications of KCl (30 mM) increased by 9-fold the firing rate of locus coeruleus cells. Perfusion with the GABA(A) receptor antagonist picrotoxin (100 microM) increased KCl-evoked effect, whereas NMDA and non-NMDA glutamate receptor antagonists (D-AP5 100 microM and CNQX 30 microM, respectively) were able to decrease KCl-evoked effect only in the presence of picrotoxin (100 microM). Bath application of WIN 55212-2 (10 microM) inhibited KCl-evoked effect; this inhibition was blocked by the CB(1) receptor antagonist AM 251 (1 microM). However, a lower concentration of WIN 55212-2 (1 microM) did not significantly change KCl effect. In the presence of picrotoxin (100 microM), perfusion with D-AP5 (100 microM) or CNQX (30 microM) blocked WIN 55212-2-induced inhibition, although picrotoxin (100 microM) itself failed to affect cannabinoid effect. In conclusion, GABAergic and glutamatergic components are both involved in KCl-evoked excitation of LC neurons, although CB(1) receptors only seem to inhibit the glutamatergic component of KCl effect in the locus coeruleus.

PMID: 17070872 [PubMed - indexed for MEDLINE]

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Friday, 6 April 2007

Nicotinics and WM

Distributed Network Actions by Nicotine Increase the Threshold for Spike-Timing-Dependent Plasticity in Prefrontal Cortex.


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Distributed Network Actions by Nicotine Increase the Threshold for Spike-Timing-Dependent Plasticity in Prefrontal Cortex.

Neuron. 2007 Apr 5;54(1):73-87

Authors: Couey JJ, Meredith RM, Spijker S, Poorthuis RB, Smit AB, Brussaard AB, Mansvelder HD

Nicotine enhances attention and working memory by activating nicotinic acetylcholine receptors (nAChRs). The prefrontal cortex (PFC) is critical for these cognitive functions and is also rich in nAChR expression. Specific cellular and synaptic mechanisms underlying nicotine's effects on cognition remain elusive. Here we show that nicotine exposure increases the threshold for synaptic spike-timing-dependent potentiation (STDP) in layer V pyramidal neurons of the mouse PFC. During coincident presynaptic and postsynaptic activity, nicotine reduces dendritic calcium signals associated with action potential propagation by enhancing GABAergic transmission. This results from a series of presynaptic actions involving different PFC interneurons and multiple nAChR subtypes. Pharmacological block of nAChRs or GABA(A) receptors prevented nicotine's actions and restored STDP, as did increasing dendritic calcium signals with stronger postsynaptic activity. Thus, by activating nAChRs distributed throughout the PFC neuronal network, nicotine affects PFC information processing and storage by increasing the amount of postsynaptic activity necessary to induce STDP.

PMID: 17408579 [PubMed - as supplied by publisher]

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Cerebellum & Ca2+

Plasma Membrane Ca2+ ATPase 2 Contributes to Short-Term Synapse Plasticity at the Parallel Fiber to Purkinje Neuron Synapse

Plasma membrane Ca2+ ATPase 2 (PMCA2) is a fast, highly effective mechanism to control resting cytosolic Ca2+ and Ca2+ excursions in neurons and other excitable cells. The strong expression of PMCA2 in the cerebellum and the cerebe

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