01-10-2016, 03:31 PM
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ABSTRACT
Today scientists are in research to create an artificial brain that can think, respond, take decision, and keep anything in memory. The main aim is to upload human brain into machine. So that man can think, take decision without any effort. After the death of the body, the virtual brain will act as the man. So, even after the death of a person we will not loose the knowledge, intelligence, personalities, feelings and memories of that man, that can be used for the development of the human society. Technology is growing faster than every thing. IBM is now in research to create a virtual brain, called “Blue brain”. If possible, this would be the first virtual brain of the world. IBM, in partnership with scientists at Switzerland’s Ecole Polytech-nique Federale de Lausanne’s (EPFL) Brain and Mind Institute will begin simulating the brain’s biological systems and output the data as a working 3-dimensional model that will recreate the high-speed electro-chemical interactions that take place within the brain’s interior. These include cognitive functions such as language, learning, perception and memory in addition to brain malfunction such as psychiatric disorders like depression and autism. From there, the modeling will expand to other regions of the brain and, if successful, shed light on the relationships between genetic, molecular and cognitive functions of the brain.
INTRODUCTION
Human brain is the most valuable creation of God. The man is called intelligent because of the brain. The brain translates the information delivered by the impulses, which then enables the person to react. But we loss the knowledge of a brain when the body is destroyed after the death of man. That knowledge might have been used for the development of the human society. What happen if we create a brain and up load the contents of natural brain into it?
1.1 Blue Brain
The name of the world’s first virtual brain. That means a machine that can function as human brain. Today scientists are in research to create an artificial brain that can think, response, take decision, and keep anything in memory. The main aim is to upload human brain into machine. So that man can think, take decision without any effort. After the death of the body, the virtual brain will act as the man .So, even after the death of a person we will not loose the knowledge, intelligence, personalities, feelings and memories of that man that can be used for the development of the human society. No one has ever understood the complexity of human brain. It is complex than any circuitry in the world.. IBM is now in research to create a virtual brain, called “Blue brain”. If possible, this would be the first virtual brain of the world. With in 30 years, we will be able to scan ourselves into the computers. Is this the beginning of eternal life?
1
1.2 What is Virtual Brain?
Virtual brain is an artificial brain, which does not actually the natural brain, but can act as the brain. It can think like brain, take decisions based on the past experience, and response as the natural brain can. It is possible by using a super computer, with a huge amount of storage capacity, processing power and an interface between the human brain and this artificial one. Through this interface the data stored in the natural brain can be up loaded into the computer. So the brain and the knowledge, intelligence of anyone can be kept and used for ever, even after the death of the person.
1.3 Why we need Virtual Brain?
Today we are developed because of our intelligence. Intelligence is the inborn quality that can not be created. Some people have this quality, so that they can think up to such an extent where other can not reach. Human society is always need of such intelligence and such an intelligent brain to have with. But the intelligence is lost along with the body after the death. The virtual brain is a solution to it. The brain and intelli-gence will alive even after the death. We often face difficulties in remembering things such as people’s names, their birthdays, and the spellings of words, proper grammar, important dates, history, facts etc... In the busy life every one want to be relaxed. Can’t we use any machine to assist for all these? Virtual brain may be the solution to it. What if we upload ourselves into computer, we were simply aware of a computer, or maybe, what if we lived in a computer as a program?
1.4 How it is possible?
First, it is helpful to describe the basic manners in which a person may be uploaded into a computer. Raymond Kurzweil recently provided an interesting paper on this topic. In it, he describes both invasive and noninvasive techniques. The most promising is the use of very small robots, or nanobots. These robots will be small enough to travel throughout our circulatory systems. Traveling into the spine and brain, they will be able to monitor the activity and structure of our central nervous system.
2
They will be able to provide an interface with computers that is as close as our mind can be while we still reside in our biological form. Nanobots could also carefully scan the structure of our brain, providing a complete readout of the connections between each neuron. They would also record the current state of the brain. This information, when entered into a computer, could then continue to function as us. All that is required is a computer with large enough storage space and processing power. Is the pattern and state of neuron connections in our brain truly all that makes up our conscious selves? Many people believe firmly those we posses a soul, while some very technical people believe that quantum forces contribute to our awareness. But we have to now think technically. Note, however, that we need not know how the brain actually functions, to transfer it to a computer. We need only know the media and contents. The actual mystery of how we achieved consciousness in the first place, or how we maintain it, is a separate discussion. Really this concept appears to be very difficult and complex to us. For this we have to first know how the human brain actually works.
WORKING OF NATURAL BRAIN
2.1 Getting to know more about Human Brain
The brain essentially serves as the body’s information processing centre. It receives signals from sensory neurons (nerve cell bodies and their axons and dendrites) in the central and peripheral nervous systems, and in response it generates and sends new signals that instruct the corresponding parts of the body to move or react in some way. It also integrates signals received from the body with signals from adjacent areas of the brain, giving rise to perception and consciousness. The brain weighs about 1,500 grams (3 pounds) and constitutes about 2 percent of total body weight. It consists of three major divisions;
The massive paired hemispheres of the cerebrum
The brainstem, consisting of the thalamus, hypothalamus, epithalamus, subtha-lamus, midbrain, pons, and medulla oblongata
The cerebellum.
The human ability to feel, interpret and even see is controlled, in computer like calculations, by the magical nervous system.The nervous system is quite like magic because we can’t see it, but its working through electric impulses through your body. One of the worlds most “intricately organized” electron mechanisms is the nervous system. Not even engineers have come close to making circuit boards and computers as delicate and precise as the nervous system. To understand this system, one has to know the three simple functions that it puts into action; sensory input, integration & motor output.
2.1.1 Sensory Input
When our eyes see something or our hands touch a warm surface, the sensory cells, also known as Neurons, send a message straight to your brain. This action of getting information from your surrounding environment is called sensory input because we are putting things in your brain by way of your senses.
2.1.2 Integration
Integration is best known as the interpretation of things we have felt, tasted, and touched with our sensory cells, also known as neurons, into responses that the body recognizes. This process is all accomplished in the brain where many, many neurons work together to understand the environment.
2.1.3 Motor Output
Once our brain has interpreted all that we have learned, either by touching, tasting, or using any other sense, then our brain sends a message through neurons to effecter cells, muscle or gland cells, which actually work to perform our requests and act upon our environment.
5
2.2 How we see, hear, feel, & smell?
2.2.1 Nose
Once the smell of food has reached your nose, which is lined with hairs, it travels to an olfactory bulb, a set of sensory nerves. The nerve impulses travel through the olfactory tract, around, in a circular way, the thalamus, and finally to the smell sensory cortex of our brain, located between our eye and ear, where it is interpreted to be understood and memorized by the body.
2.2.2 Eye
Seeing is one of the most pleasing senses of the nervous system. This cherished action primarily conducted by the lens, which magnifies a seen image, vitreous disc, which bends and rotates an image against the retina, which translates the image and light by a set of cells. The retina is at the back of the eye ball where rods and cones structure along with other cells and tissues covert the image into nerve impulses which are transmitted along the optic nerve to the brain where it is kept for memory.
2.2.3 Tongue
A set of microscopic buds on the tongue divide everything we eat and drink into four kinds of taste: bitter, sour, salty, and sweet. These buds have taste pores, which convert the taste into a nerve impulse and send the impulse to the brain by a sensory nerve fiber. Upon receiving the message, our brain classifies the different kinds of taste. This is how we can refer the taste of one kind of food to another.
2.2.4 Ear
Once the sound or sound wave has entered the drum, it goes to a large structure called the cochlea. In this snail like structure, the sound waves are divided into pitches. The vibrations of the pitches in the cochlea are measured by the Corti. This organ transmits the vibration information to a nerve, which sends it to the brain for interpre-tation and memory.
HOW THE BLUE BRAIN PROJECT WILL WORK?
4.1 Goals & Objectives
The Blue Brain Project is the first comprehensive attempt to reverse-engineer the mammalian brain, in order to understand brain function and dysfunction through detailed simulations. The mission in undertaking The Blue Brain Project is to gather all existing knowledge of the brain, accelerate the global research effort of reverse engineering the structure and function of the components of the brain, and to build a complete theoretical framework that can orchestrate the reconstruction of the brain of mammals and man from the genetic to the whole brain levels, into computer models for simulation, visualization and automatic knowledge archiving by 2015. Biologi-cally accurate computer models of mammalian and human brains could provide a new foundation for understanding functions and malfunctions of the brain and for a new generation of information-based, customized medicine.
4.2 Architecture of Blue Gene
Blue Gene/L is built using system-on-a-chip technology in which all functions of a node (except for main memory) are integrated onto a single application-specific integrated circuit (ASIC). This ASIC includes 2 PowerPC 440 cores running at 700 MHz. Associated with each core is a 64-bit “double” floating point unit (FPU) that can operate in single instruction, multiple data (SIMD) mode. Each (single) FPU can execute up to 2 “multiply-adds” per cycle, which means that the peak performance of the chip is 8 floating point operations per cycle (4 under normal conditions, with no use of SIMD mode). This leads to a peak performance of 5.6 billion floating point operations per second (gigaFLOPS or GFLOPS) per chip or node, or 2.8 GFLOPS
9
in non- SIMD mode. The two CPUs (central processing units) can be used in “co-processor” mode (resulting in one CPU and 512 MB RAM (random access memory) for computation, the other CPU being used for processing the I/O (input/output) of the main CPU) or in “virtual node” mode (in which both CPUs with 256 MB each are used for computation). So, the aggregate performance of a processor card in virtual node mode is: 2 x node = 2 x 2.8 GFLOPS = 5.6 GFLOPS, and its peak performance (optimal use of double FPU) is: 2 x 5.6 GFLOPS = 11.2 GFLOPS. A rack (1,024 nodes = 2,048 CPUs) therefore has 2.8 teraFLOPS or TFLOPS, and a peak of 5.6 TFLOPS. The Blue Brain Projects Blue Gene is a 4-rack system that has 4,096 nodes, equal to 8,192 CPUs, with a peak performance of 22.4 TFLOPS. A 64-rack machine should provide 180 TFLOPS, or 360 TFLOPS at peak performance.
4.3 Modelling the Microcircuit
The scheme shows the minimal essential building blocks required to recon-struct a neural microcircuit. Microcircuits are composed of neurons and synaptic connections. To model neurons, the three-dimensional morphology, ion channel composition, and distributions and electrical properties of the different types of neuron are required, as well as the total numbers of neurons in the microcircuit and the relative proportions of the different types of neuron. To model synaptic connections, the physiological and pharmacological properties of the different types of synapse that connect any two types of neuron are required, in addition to statistics on which part of the axonal arborization is used (presynaptic innervation pattern) to contact which regions of the target neuron (postsynaptic innervations pattern), how many synapses are involved in forming connections, and the connectivity statistics between any two types of neuron. Neurons receive inputs from thousands of other neurons, which are intricately mapped onto different branches of highly complex dendritic trees and require tens of thousands of compartments to accurately represent them. There is therefore a minimal size of a microcircuit and a minimal complexity of a neuron’s morphology that can fully sustain a neuron. A massive increase in computational power is required to make this quantum leap - an increase that is provided by IBM’s Blue Gene supercomputer. By exploiting the computing power of Blue Gene, the Blue Brain Project1 aims to build accurate models of the mammalian brain from first principles. The first phase of the project is to build a cellular-level (as opposed to a genetic- or molecular-level) model of a 2-week-old rat somatosensory neocortex corresponding to the dimensions of a neocortical column (NCC) as defined by the dendritic arborizations of the layer 5 pyramidal neurons. The combination of infrared differential interference microscopy in brain slices and the use of multi-neuron patch-
11
clamping allowed the systematic quantification of the molecular, morphological and electrical properties of the different neurons and their synaptic pathways in a manner that would allow an accurate reconstruction of the column. Over the past 10 years, the laboratory has prepared for this reconstruction by developing the multi-neuron patch-clamp approach, recording from thousands of neocortical neurons and their synaptic connections, and developing quantitative approaches to allow a complete numerical breakdown of the elementary building blocks of the NCC. The recordings have mainly been in the 14-16-day-old rat somatosensory cortex, which is a highly accessible region on which many researchers have converged following a series of pioneering studies driven by Bert Sakmann. Much of the raw data is located in our databases, but a major initiative is underway to make all these data freely available in a publicly accessible database. The so-called ’blue print’ of the circuit, although not entirely complete, has reached a sufficient level of refinement to begin the reconstruction at the cellular level. Highly quantitative data are available for rats of this age, mainly because visualization of the tissue is optimal from a technical point of view. This age also provides an ideal template because it can serve as a starting point from which to study maturation and ageing of the NCC. As NCCs show a high degree of stereotypy, the region from which the template is built is not crucial, but a sensory region is preferred because these areas contain a prominent layer 4 with cells specialized to receive input to the neocortex from the thalamus; this will also be required for later calibration with in vivo experiments. The NCC should not be overly specialized, because this could make generalization to other neocortical regions difficult, but areas such as the barrel cortex do offer the advantage of highly controlled in vivo data for comparison. The mouse might have been the best species to begin with, because it offers a spectrum of molecular approaches with which to explore the circuit, but mouse neurons are small, which prevents the detailed dendritic recordings that are important for modelling the nonlinear properties of the complex dendritic trees of pyramidal cells (75-80% of the neurons). The image shows the Microcircuit in various stages of reconstruction. Only a small fraction of reconstructed, three dimensional neurons is shown. Red indicates the dendritic and blue the axonal arborizations. The columnar structure illustrates the layer definition of the NCC.
The microcircuits (from left to right) for layers 2, 3, 4 and 5.
A single thick tufted layer 5 pyramidal neuron located within the column.
One pyramidal neuron in layer 2, a small pyramidal neuron in layer 5 and the large thick tufted pyramidal neuron in layer
An image of the NCC, with neurons located in layers 2 to 5.
ABSTRACT
Today scientists are in research to create an artificial brain that can think, respond, take decision, and keep anything in memory. The main aim is to upload human brain into machine. So that man can think, take decision without any effort. After the death of the body, the virtual brain will act as the man. So, even after the death of a person we will not loose the knowledge, intelligence, personalities, feelings and memories of that man, that can be used for the development of the human society. Technology is growing faster than every thing. IBM is now in research to create a virtual brain, called “Blue brain”. If possible, this would be the first virtual brain of the world. IBM, in partnership with scientists at Switzerland’s Ecole Polytech-nique Federale de Lausanne’s (EPFL) Brain and Mind Institute will begin simulating the brain’s biological systems and output the data as a working 3-dimensional model that will recreate the high-speed electro-chemical interactions that take place within the brain’s interior. These include cognitive functions such as language, learning, perception and memory in addition to brain malfunction such as psychiatric disorders like depression and autism. From there, the modeling will expand to other regions of the brain and, if successful, shed light on the relationships between genetic, molecular and cognitive functions of the brain.
INTRODUCTION
Human brain is the most valuable creation of God. The man is called intelligent because of the brain. The brain translates the information delivered by the impulses, which then enables the person to react. But we loss the knowledge of a brain when the body is destroyed after the death of man. That knowledge might have been used for the development of the human society. What happen if we create a brain and up load the contents of natural brain into it?
1.1 Blue Brain
The name of the world’s first virtual brain. That means a machine that can function as human brain. Today scientists are in research to create an artificial brain that can think, response, take decision, and keep anything in memory. The main aim is to upload human brain into machine. So that man can think, take decision without any effort. After the death of the body, the virtual brain will act as the man .So, even after the death of a person we will not loose the knowledge, intelligence, personalities, feelings and memories of that man that can be used for the development of the human society. No one has ever understood the complexity of human brain. It is complex than any circuitry in the world.. IBM is now in research to create a virtual brain, called “Blue brain”. If possible, this would be the first virtual brain of the world. With in 30 years, we will be able to scan ourselves into the computers. Is this the beginning of eternal life?
1
1.2 What is Virtual Brain?
Virtual brain is an artificial brain, which does not actually the natural brain, but can act as the brain. It can think like brain, take decisions based on the past experience, and response as the natural brain can. It is possible by using a super computer, with a huge amount of storage capacity, processing power and an interface between the human brain and this artificial one. Through this interface the data stored in the natural brain can be up loaded into the computer. So the brain and the knowledge, intelligence of anyone can be kept and used for ever, even after the death of the person.
1.3 Why we need Virtual Brain?
Today we are developed because of our intelligence. Intelligence is the inborn quality that can not be created. Some people have this quality, so that they can think up to such an extent where other can not reach. Human society is always need of such intelligence and such an intelligent brain to have with. But the intelligence is lost along with the body after the death. The virtual brain is a solution to it. The brain and intelli-gence will alive even after the death. We often face difficulties in remembering things such as people’s names, their birthdays, and the spellings of words, proper grammar, important dates, history, facts etc... In the busy life every one want to be relaxed. Can’t we use any machine to assist for all these? Virtual brain may be the solution to it. What if we upload ourselves into computer, we were simply aware of a computer, or maybe, what if we lived in a computer as a program?
1.4 How it is possible?
First, it is helpful to describe the basic manners in which a person may be uploaded into a computer. Raymond Kurzweil recently provided an interesting paper on this topic. In it, he describes both invasive and noninvasive techniques. The most promising is the use of very small robots, or nanobots. These robots will be small enough to travel throughout our circulatory systems. Traveling into the spine and brain, they will be able to monitor the activity and structure of our central nervous system.
2
They will be able to provide an interface with computers that is as close as our mind can be while we still reside in our biological form. Nanobots could also carefully scan the structure of our brain, providing a complete readout of the connections between each neuron. They would also record the current state of the brain. This information, when entered into a computer, could then continue to function as us. All that is required is a computer with large enough storage space and processing power. Is the pattern and state of neuron connections in our brain truly all that makes up our conscious selves? Many people believe firmly those we posses a soul, while some very technical people believe that quantum forces contribute to our awareness. But we have to now think technically. Note, however, that we need not know how the brain actually functions, to transfer it to a computer. We need only know the media and contents. The actual mystery of how we achieved consciousness in the first place, or how we maintain it, is a separate discussion. Really this concept appears to be very difficult and complex to us. For this we have to first know how the human brain actually works.
WORKING OF NATURAL BRAIN
2.1 Getting to know more about Human Brain
The brain essentially serves as the body’s information processing centre. It receives signals from sensory neurons (nerve cell bodies and their axons and dendrites) in the central and peripheral nervous systems, and in response it generates and sends new signals that instruct the corresponding parts of the body to move or react in some way. It also integrates signals received from the body with signals from adjacent areas of the brain, giving rise to perception and consciousness. The brain weighs about 1,500 grams (3 pounds) and constitutes about 2 percent of total body weight. It consists of three major divisions;
The massive paired hemispheres of the cerebrum
The brainstem, consisting of the thalamus, hypothalamus, epithalamus, subtha-lamus, midbrain, pons, and medulla oblongata
The cerebellum.
The human ability to feel, interpret and even see is controlled, in computer like calculations, by the magical nervous system.The nervous system is quite like magic because we can’t see it, but its working through electric impulses through your body. One of the worlds most “intricately organized” electron mechanisms is the nervous system. Not even engineers have come close to making circuit boards and computers as delicate and precise as the nervous system. To understand this system, one has to know the three simple functions that it puts into action; sensory input, integration & motor output.
2.1.1 Sensory Input
When our eyes see something or our hands touch a warm surface, the sensory cells, also known as Neurons, send a message straight to your brain. This action of getting information from your surrounding environment is called sensory input because we are putting things in your brain by way of your senses.
2.1.2 Integration
Integration is best known as the interpretation of things we have felt, tasted, and touched with our sensory cells, also known as neurons, into responses that the body recognizes. This process is all accomplished in the brain where many, many neurons work together to understand the environment.
2.1.3 Motor Output
Once our brain has interpreted all that we have learned, either by touching, tasting, or using any other sense, then our brain sends a message through neurons to effecter cells, muscle or gland cells, which actually work to perform our requests and act upon our environment.
5
2.2 How we see, hear, feel, & smell?
2.2.1 Nose
Once the smell of food has reached your nose, which is lined with hairs, it travels to an olfactory bulb, a set of sensory nerves. The nerve impulses travel through the olfactory tract, around, in a circular way, the thalamus, and finally to the smell sensory cortex of our brain, located between our eye and ear, where it is interpreted to be understood and memorized by the body.
2.2.2 Eye
Seeing is one of the most pleasing senses of the nervous system. This cherished action primarily conducted by the lens, which magnifies a seen image, vitreous disc, which bends and rotates an image against the retina, which translates the image and light by a set of cells. The retina is at the back of the eye ball where rods and cones structure along with other cells and tissues covert the image into nerve impulses which are transmitted along the optic nerve to the brain where it is kept for memory.
2.2.3 Tongue
A set of microscopic buds on the tongue divide everything we eat and drink into four kinds of taste: bitter, sour, salty, and sweet. These buds have taste pores, which convert the taste into a nerve impulse and send the impulse to the brain by a sensory nerve fiber. Upon receiving the message, our brain classifies the different kinds of taste. This is how we can refer the taste of one kind of food to another.
2.2.4 Ear
Once the sound or sound wave has entered the drum, it goes to a large structure called the cochlea. In this snail like structure, the sound waves are divided into pitches. The vibrations of the pitches in the cochlea are measured by the Corti. This organ transmits the vibration information to a nerve, which sends it to the brain for interpre-tation and memory.
HOW THE BLUE BRAIN PROJECT WILL WORK?
4.1 Goals & Objectives
The Blue Brain Project is the first comprehensive attempt to reverse-engineer the mammalian brain, in order to understand brain function and dysfunction through detailed simulations. The mission in undertaking The Blue Brain Project is to gather all existing knowledge of the brain, accelerate the global research effort of reverse engineering the structure and function of the components of the brain, and to build a complete theoretical framework that can orchestrate the reconstruction of the brain of mammals and man from the genetic to the whole brain levels, into computer models for simulation, visualization and automatic knowledge archiving by 2015. Biologi-cally accurate computer models of mammalian and human brains could provide a new foundation for understanding functions and malfunctions of the brain and for a new generation of information-based, customized medicine.
4.2 Architecture of Blue Gene
Blue Gene/L is built using system-on-a-chip technology in which all functions of a node (except for main memory) are integrated onto a single application-specific integrated circuit (ASIC). This ASIC includes 2 PowerPC 440 cores running at 700 MHz. Associated with each core is a 64-bit “double” floating point unit (FPU) that can operate in single instruction, multiple data (SIMD) mode. Each (single) FPU can execute up to 2 “multiply-adds” per cycle, which means that the peak performance of the chip is 8 floating point operations per cycle (4 under normal conditions, with no use of SIMD mode). This leads to a peak performance of 5.6 billion floating point operations per second (gigaFLOPS or GFLOPS) per chip or node, or 2.8 GFLOPS
9
in non- SIMD mode. The two CPUs (central processing units) can be used in “co-processor” mode (resulting in one CPU and 512 MB RAM (random access memory) for computation, the other CPU being used for processing the I/O (input/output) of the main CPU) or in “virtual node” mode (in which both CPUs with 256 MB each are used for computation). So, the aggregate performance of a processor card in virtual node mode is: 2 x node = 2 x 2.8 GFLOPS = 5.6 GFLOPS, and its peak performance (optimal use of double FPU) is: 2 x 5.6 GFLOPS = 11.2 GFLOPS. A rack (1,024 nodes = 2,048 CPUs) therefore has 2.8 teraFLOPS or TFLOPS, and a peak of 5.6 TFLOPS. The Blue Brain Projects Blue Gene is a 4-rack system that has 4,096 nodes, equal to 8,192 CPUs, with a peak performance of 22.4 TFLOPS. A 64-rack machine should provide 180 TFLOPS, or 360 TFLOPS at peak performance.
4.3 Modelling the Microcircuit
The scheme shows the minimal essential building blocks required to recon-struct a neural microcircuit. Microcircuits are composed of neurons and synaptic connections. To model neurons, the three-dimensional morphology, ion channel composition, and distributions and electrical properties of the different types of neuron are required, as well as the total numbers of neurons in the microcircuit and the relative proportions of the different types of neuron. To model synaptic connections, the physiological and pharmacological properties of the different types of synapse that connect any two types of neuron are required, in addition to statistics on which part of the axonal arborization is used (presynaptic innervation pattern) to contact which regions of the target neuron (postsynaptic innervations pattern), how many synapses are involved in forming connections, and the connectivity statistics between any two types of neuron. Neurons receive inputs from thousands of other neurons, which are intricately mapped onto different branches of highly complex dendritic trees and require tens of thousands of compartments to accurately represent them. There is therefore a minimal size of a microcircuit and a minimal complexity of a neuron’s morphology that can fully sustain a neuron. A massive increase in computational power is required to make this quantum leap - an increase that is provided by IBM’s Blue Gene supercomputer. By exploiting the computing power of Blue Gene, the Blue Brain Project1 aims to build accurate models of the mammalian brain from first principles. The first phase of the project is to build a cellular-level (as opposed to a genetic- or molecular-level) model of a 2-week-old rat somatosensory neocortex corresponding to the dimensions of a neocortical column (NCC) as defined by the dendritic arborizations of the layer 5 pyramidal neurons. The combination of infrared differential interference microscopy in brain slices and the use of multi-neuron patch-
11
clamping allowed the systematic quantification of the molecular, morphological and electrical properties of the different neurons and their synaptic pathways in a manner that would allow an accurate reconstruction of the column. Over the past 10 years, the laboratory has prepared for this reconstruction by developing the multi-neuron patch-clamp approach, recording from thousands of neocortical neurons and their synaptic connections, and developing quantitative approaches to allow a complete numerical breakdown of the elementary building blocks of the NCC. The recordings have mainly been in the 14-16-day-old rat somatosensory cortex, which is a highly accessible region on which many researchers have converged following a series of pioneering studies driven by Bert Sakmann. Much of the raw data is located in our databases, but a major initiative is underway to make all these data freely available in a publicly accessible database. The so-called ’blue print’ of the circuit, although not entirely complete, has reached a sufficient level of refinement to begin the reconstruction at the cellular level. Highly quantitative data are available for rats of this age, mainly because visualization of the tissue is optimal from a technical point of view. This age also provides an ideal template because it can serve as a starting point from which to study maturation and ageing of the NCC. As NCCs show a high degree of stereotypy, the region from which the template is built is not crucial, but a sensory region is preferred because these areas contain a prominent layer 4 with cells specialized to receive input to the neocortex from the thalamus; this will also be required for later calibration with in vivo experiments. The NCC should not be overly specialized, because this could make generalization to other neocortical regions difficult, but areas such as the barrel cortex do offer the advantage of highly controlled in vivo data for comparison. The mouse might have been the best species to begin with, because it offers a spectrum of molecular approaches with which to explore the circuit, but mouse neurons are small, which prevents the detailed dendritic recordings that are important for modelling the nonlinear properties of the complex dendritic trees of pyramidal cells (75-80% of the neurons). The image shows the Microcircuit in various stages of reconstruction. Only a small fraction of reconstructed, three dimensional neurons is shown. Red indicates the dendritic and blue the axonal arborizations. The columnar structure illustrates the layer definition of the NCC.
The microcircuits (from left to right) for layers 2, 3, 4 and 5.
A single thick tufted layer 5 pyramidal neuron located within the column.
One pyramidal neuron in layer 2, a small pyramidal neuron in layer 5 and the large thick tufted pyramidal neuron in layer
An image of the NCC, with neurons located in layers 2 to 5.