CSB332 Lecture 2 Notes

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Cell and Systems Biology
Francis Bambico

CSB332 Lecture 2 Slide 3 - Neuroanatomy refers to the mapping of the different parts and structures of the brain with its associated functions. - These are the different subdivisions of the brain. The brain is subdivided into three general subdivisions, organized from an inferior to superior direction. The hindbrain is the lowest part of the brain. The forebrain is the most superior and the most upper part of the brain. - Hindbrain o Medulla oblongata  Closest to the spinal cord o Pons and cerebellum collectively are termed the metencephalon  Can be localized based on the location of the fourth ventricle, which is the most caudal or lowest ventricular recess in the brain that is filled with CSF and is located between the cerebellum and the pons o Cerebellum  Controls voluntary or coordinated movement of gait and eye movement  Cerebellum ataxia is a lesion in the cerebellum, which is the incoordination of voluntary movement  Contains as much neurons that is contained in the cerebrum or the rest of the brain o Pons  In front of the cerebellum  Bridges fibres or bundles of axons that project from the cerebral cortex to the cerebellum  Contains fibres that bridges axons from the cerebrum to the cerebellum by a cortico ponto cerebellar pathway - Midbrain o Tectum  Subdivided into the superior colliculi (visual system) and inferior colliculi (auditory system)  Involved in visual and auditory modalities o Tegmentum - Forebrain o Diencephalon  Hypothalamus • Involved in motivation and physiological processes • Controls the four F’s of motivated behaviour (stress response, flight and fight response, feeding, fleeing, fighting, and fucking)  Thalamus • Involved in relaying sensory information • Sensory information is first received by sensory neurons, which relay information to the thalamus before the information is delivered to the cerebral cortices • Main sensory relay station of the brain • Two egg-shaped structures connected by fibres called the interthalamic adhesion, which leaves a recess in the middle. The recess in the middle corresponds to the third ventricle. The third ventricle is sandwiched between the two thalamic lobes superiorly. The third ventricle is also sandwiched by the hypothalamus inferiorly. o Telencephalon  The latest addition to the evolution of the mammalian brain, particularly the cerebral cortex.  Subcortical regions • Beneath the cerebral cortex that wraps around the lateral ventricle • Limbic system o Involved in memory and emotion regulation o Contains important nuclei (structures of cell bodies) that process memory and emotion regulation  Hippocampus is responsible for memory  Amygdala is responsible for fear response  Cingulate cortex  Nucleus accumbens is responsible for pleasurable experiences • Basal ganglia o Involved in motor functions  Cerebral cortex • Convoluted part of the brain • Gyrus = ridge on the cerebral cortex o More superficial layers of the cerebral cortex contain cell bodies, which project axons downwards to form the white matter • Sulcus or fissures = depression on the cerebral cortex • Processes many complex functions (e.g., thinking, problem solving, decision making, planning) - The functions of the brain are organized according to o Hierarchy  The more superior structures control more complex functions.  The most caudal part of the brain is involved in basic, vital processes. o Laterality  In the cerebral cortex, there are specific functions controlled in the right hemisphere (e.g., spatial orientation, navigation) of the brain and there are specific functions that are associated with the left hemisphere (e.g., language, mathematical ability, processing of positive emotional experiences) the brain. o Modularity  Within the hemispheres, you can pinpoint specific gyri or specific regions that control very specific functions.  Broca’s area controls the motor function of language  Wernicke’s area is located in the posterior aspect of the superior temporal gyrus - There are four lobes of the brain (frontal, parietal, occipital, temporal, and limbic) that are separated by large sulci or fissures. Slide 4 - The subarachnoid space is filled with CSF, and is beneath the arachnoid matter and above the pia mater. This is where the CSF is drained out from the ventricular system. CSF is constantly replenished. CSF exits the ventricular system and engorges the entire brain. The brain is suspended in CSF. The exit point for CSF is called foramen. CSF exits into the subarachnoid space. - The arachnoid mater is the second layer of the meninges. The meninges are the external protective cover of the brain that is composed of three layers (dura mater, arachnoid mater, pia mater). The pia mater is closest to the surface of the brain. - The third and fourth ventricles are connected by the cerebral aqueduct. - Hippocampus can be identified using the midsagittal cut because it is buried deep within the hippocampal gyrus in the medial temporal lobe. Amygdala is in front of the hippocampus, just beneath the hippocampal gyrus. - The basal ganglia and limbic system surrounds the third ventricle and the lateral ventricle. The lateral ventricle is located just beneath the corpus callosum. - The septum pellucidum is a thin membrane separates the left and right lateral ventricles. Slide 5 - Intelligence is associated not with the size of the brain, but the size of the neocortex in comparison to the rest of the body. The brain body index determines if one species is more intelligent than another species (e.g., whales and dolphins have a high brain body index). One exception is the shrew rat, which has a high brain body index but isn’t intelligent. - There are two methods of imaging the topography of the brain: MRI and PET. o MRI  Ability to distinguish between white matter, gray matter, and CSF.  Applying a magnetic field will align the protons towards a north/south direction, or an antiparallel/parallel direction according to the polarity of the magnetic field that is applied in the scanner. As a result, you produce a strong, longitudinal magnetic vector.  Applying a RF pulse will disorient or dislodge some of the hydrogen protons, which will reorient towards a horizontal or transverse axis. The net longitudinal magnetic vector would go down. • You get attenuation of the net longitudinal magnetic vector. • You get a buildup of a transverse or horizontal net magnetic field vector.  If you withdraw the RF pulse, the hydrogen protons that got dislodged would re-establish their orientation towards the north/south direction. • The transverse field vector would decrease or get attenuated. The time course of the decrease or attenuation of the transverse net magnetic field vector is called the T2 relaxation time. The T2 relaxation time varies according to the type of tissue. The T2 relaxation time for CSF is highest, followed by gray matter, and white matter is the lowest. • The longitudinal field vector would be re-establish its peak, or gradually increase. The gradual increase of the net longitudinal field vector is called the T1 relaxation time. The T1 relaxation time is different for different substances in the brain.  The MRI image is based on the T1 relaxation times. In the T1 weighted image, white matter emits the strongest T1 signal, followed by gray matter, and CSF emits the lowest T1 signal.  T2 weighted image is used for fMRI. fMRI makes use of T2 signal from oxygen in the brain (e.g., the difference in the T2 signal between the deoxygenated blood in comparison to the oxygenated blood). • The red blot is a T2 weighted signal comparing the T2 relaxation signal from an oxygenated blood in comparison to deoxygenated blood. There is a heavy perfusion of oxygenated blood in this part of the brain, which is the amygdala. Slide 6 - He is suffering from some type of dementia or Alzheimer’s because there is a global decline of many cognitive functions. There is a global degeneration of many regions of the brain. o Impulse controls  frontal lobe o Impairments of sexual activity  hypothalamus, dopamine producing neurons, nucleus accumbens o Memory loss  hippocampus o Motor problems  basal ganglia, motor cortices in the cerebral cortex Slide 7 - The basal ganglia motor complex might have disappeared. Slide 8 - The cerebral tissue might be punctuated by clusters or proteins (e.g., buildup of plaques). Amyloid beta proteins are abnormally folded in the cerebral cortices of person suffering from AD patient. Beta amyloid plaques characterize the tissue of an AD patient. Slide 9 - What imaging tool can you use with these radioactive substances? o PET involves the injection of the compounds into the carotid artery. Since these compounds bind beta amyloid proteins, you would be able to detect the positrons being emitted by these compounds. The radioactive isotopes would emit positrons. When the positrons encounter electrons, the annihilation reaction will produce gamma photons. The gamma photons are being detected and located by the PET scanner. - A directly affected neurotransmitter system in dementia or Alzheimer’s disease is the degeneration of cholinergic system. If you are interested in reversing dysfunctions in the degeneration of the cholinergic neurons, what approach is a good way of testing the effect of the treatment? o You need to know where the neurons and synapses are in the brain using immunohistochemistry (ex vivo; antibodies against specific components of the cholinergic neurons; antibodies are tagged with fluorophore or chromogen or a compound that changes colour when it reacts with another compound), in situ hybridization, etc. o In live animals (in vivo), you can use transgenic mice (knockout of the components of the cholinergic neurons), or visualize dendritic spines or changes in synaptic density using two-photon imaging (to visualize changes in live animals; related to confocal microscopy which uses high energy photons; uses two low energy photons that when summed up, it achieves excitation frequency; two low energy photons will not damage the cell as much as high energy photons). Slide 10 - These are stains for non-specific things o Basophilic stain  Stain the cell bodies of cholinergic neurons, for example. The molecules are basic or alkaline, and bind acidic components in the cell body (e.g., nucleic acids).  Primarily stain the cell body  Modestly stain neuritic processes that emanate from the cell bodies o Fiber stain  Stain specific compounds o Golgi stain  Stain the entire structure of the neuron - Intracellular and juxtacellular labeling o Stain a specific group of neurons o Use antibodies raised against specific components that are specific to the neuron of interest o Use antisense nucleotide probes tagged with something you can see to stain mRNA transcripts of the components in the neurons  Fluorophores  Chromogenic molecules change colour when it reacts with another compound  Radioactive labels • Autoradiography makes use of ligands bound to radioactive labels, and radioactivity is detected with other techniques - In situ hybridization o To locate cell bodies of cholinergic neurons o To visualize where the transmitters are being produced o To see if the neurons are degraded compared to a model o Use to visualize the mRNA of vesicular transporters for acetylcholine - Immunohistochemistry o Use to visualize acetylcholinesterase because it is synthesized in the nerve terminals o To visualize transmitters in the axon terminals (e.g., antibodies raised against the transmitters) Slide 11 - Small molecule neurotransmitters (e.g., biogenic amides, monoamines, ACh) are synthesized de novo in the nerve terminals, so you cannot find them in the cell bodies. If you want to localize the cell bodies that produce those neurons, then you have to use other probes. - Neuropeptides are large molecule neurotransmitters. The precursors of neuropeptides are synthesized in the cell bodies. You can use ISH and immunohistochemistry to visualize the precursors of the neuropeptides in the cell bodies. Once the precursors
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