X-Message-Number: 26916 From: Date: Fri, 2 Sep 2005 10:00:50 EDT Subject: Uploading technology (1.vii.1) Channel diversity (3 fast chemical). Uploading technology (1.vii.1) Channel diversity (3 fast chemical). These receptors act with a time constant near 2.7 ms. Some are excitatory, that is, depolarising, other are inhibitory or hyperpolarising. There are two receptor famillies, based on biochemical similarities : 1 / The firsts include the nicotinic (reacting to the tobaco nicotine alcaloid) acethylcholine recedptors, the nAChR for short, the gamma aminobuthyric acid receptors of the A kind (GABA-A), the Glycine receptor (GlyR) and some serotonin receptors. 2 / The second familly include the excitatory glutamate receptors (GluR). Serotonin and ACh are cation sensitive they have a permeability to Na+, K+ or Ca++. On the anion side, Cl-, there is Gly and GABA-A. In the human species, there are 2 Gly receptors and 9 GABA-A for anions. On the cation side, There is one serotonin and 6 ACh. Each channel is built from 5 sub-units, for example ACh contains a mixing of two sub-unit kind : alpha and beta, there are 9 alpha variants and 3 beta. Depending on the composition, there may be hundreds of different channels. Some open or close more or less rapidly, they have different conductivity, different refractory time, and so on. For example the serotonin channel is ten time slower than the run of the mill ACh model, it has a permeability to both, Na+ and K+, that is, it first depolarise with Na+ and then repolarise with K+. Its refractory time is particularly long: From one to five seconds. If there is a set of rapid action potentials, it will react only to the first, the others falls in the refractory time. The refractory time, depending on the sub-unit composition, may be anywhere between 100 ms and 20 seconds. 8 values, that is 3 bits could be necessary to cover raisonably that range. Conductivity can goes from 5 to 50 pico Sievers. Four values could be useful (2 bits). The Ca++/Na+ permeability ratio may be from one to twenty. This is a sensitive parameter, it may need 8 values (3 bits) in the model. The GABA-A is build too from 5 sub-units: alpha, beta, gamma, delta and epsillon. The retina has its own sub-unit: rho. There are 6 alpha, 4 beta, 4 gamma and 2 rho. The most common receptor is built from: Two alpha-1, two beta-2 and one gamma-2. Gly receptor: 5 sub-units in the receptor, always 3 alpha and 2 beta. there are 4 alpha variants and 2 beta. ATP: Two receptor sub-types: P2X and P2Z. P2X produce a fast depolarisation and is not selective, any cation can pass it. P2Z is even less selective, it let a free passage to both, cations and anions. In a given neuron, some subtype can be expressed and not others, beyond that, the way they assemble is largely a random process. In a synapse, there may be something as 1,000 channels, so the produced current is largely a statistical admixture of the individual channel activity. A similar global current can be produced with a more reduced set. The problem of the simulated electronics synapse is that it must be able to reproduce the activity of any neuron. It must so have a complete set of possibilities even if these possibilities are mutualy exclusive in a given biological synapse. The second familly contains mostly glutamate receptors. 17 Glu receptors are known in the human species. They may be broken into 5 NMDA (N-Methyl-D-Aspartate) sensitive and 12 "others". Glutamate receptor are the main excitatory channels found in the synapses. NMDA ones are tension sensitive, that is they open only if there is a glutamate molecule and a simultaneous depolarisation. This depolarisation could come from nearby firing synapses or a back propagating action potential from the preceeding neuron firing. They are desentisized by Ca++, that is, by the ion they let enter in the cell, this is an auto-inhibitory property. Each channel has two active receptors. There are 8 kinds of the first receptor and four of the second. When these receptors are mixed in the same channel, the ionic conductivity is booster by a factor between 5 to 60, depending on the R1 and R2 kind involved. A simulation would so take into account the tension threshold of activation, the desensitivation (1 to 4, 2 bits) and the 1 to 64 ( 6 bits) condictivity range. Non-NMDA receptors are not a single group, the first lot, GluR1 to GluR4 has 4 members, each with two mRNA splicing varieties called "flip" and "flop", flop desensitize more than "flip". The steady state activity of a synapse, and so of a neuron, may rests on the relative proportion of "flip" and "flop" variants. The other are poorly defined and may have different evolutionary origins. For example, there are two receptors reacting to kainate, one of them seems unable to produce a working channel. This diversity may come from the necessity for pyramidal cells to react selectively in one way or another depending the origin of the message. One dendritic tree could use mostly one receptor with a given current profile and desensitization time and another tree from the same neuron would use another receptor. When these signals mixe at the soma, different reaction could be produced depending on the dendrite bringing the signal. In a simulation, the Glu current must have a 5 bits tag telling about the receptor having produced it. The 32 tag possibilities take into account one value for NMDA receptors and 31 possibilities for the poorly defined non-NMDA channels. There is a note of caution about the tag lenghts : The above value are good for the human species only, rodens for example have other receptors with specific properties. A neuromorphic chip for brain uploading may be used for both, a small portion of the human brain or a full or larger portion of a roden brain. It seems better to test the technology first on a 15 g brain rather than a 1.5 kg one. Producing different chips for these two possibilities would not be a good economical choice. So the neuromorphic electronics neuron must be species independent. Yvan Bozzonetti. Content-Type: text/html; charset="ISO-8859-1" [ AUTOMATICALLY SKIPPING HTML ENCODING! ] Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=26916