Lecture 1 9 3 1873 Camillo Golgi The Golgi Stain a cytological stain that randomly stains whole individual neurons He came up w reticular theory all neurons are connected in the cytoplasm thru a neuron network 1906 Golgi Stain used extensively by Santiago Ramon y Cajal He came up w neuron doctrine that found that neurons are separate entities connected thru synapses used light microscopes and silver salts Charles Sherrington also promosed that neurons are individual entities in the nervous system no syncytium instead synapses between cells Cajal o Principal of dynamic polarization Information flows in a consistent way within each neuron From dendrites to the nerve axon terminal via the axon o Principal of Connectional Specificity No cytoplasmic connection between neurons Nerve cells do not form RANDOM networks Each cell makes precise connections with other neurons via synapses In general neurons have dendrites cell body axon synaptic terminal o Dendrites contain receptors for NTs or sensory receptor proteins o Axon terminal makes synaptic contact releases NTs onto dendrties of other neurons or onto muscle cells Ganglion cell retinal bipolar cell bipolar Retinal amacrine cell mesencephalic nucleus cells monopolar Cortical pyramidal cell cerebellar purkinje cell multipolar Where do neuroransmitters act on mesencephalic nucleus cells where do other neurons make synaptic contact with these cells Cell body Where do retinal amacrine cells release neurotransmitter onto other cells from where are their synapses with other neurons formed cell body Myelin sheath insulates white matter makes signals travel faster Myelinated axons have nodes of Ranvier gaps in myelin sheath Immunostaining and GFP tagging methods localize proteins and ion channels allows to find structure of neuron Tublin microtubule binding protein uniformly distributed Actin localized to dendritic spine Acetylcholine clustered under the synaptic terminal ends of axons Lecture 2 9 5 Glial Cells Support cells o Regulate environment around nerve cells o Take up NT s released from axon terminals o Play a role in defending the brain and spinal cord against injury and infection or perversely in impeding recovery from injury o Can direct neuronal growth o Glial stem cells can proliferate and differentiate into new glial cells and in some places neurons 10 50 times more glial cells than neurons in the brain Cancer of the brain isn t cancer of the neurons its cancer of the glials See picture 1 Do glial cells transmit information in the NS Old Dogma do not carry information Now blurred but almost certainly not over large distances within the brain Certainly are vital for normal information processing e g by taking up NT s uptake blocked by psychoactive drugs o By taking up NTs they permit normal But recently astrocytes have come to be recognized as not only support cells for neurons but also as partners in fundamental neural processes Glial cell types fig 1 5 A Astrocytes Involved in potassium uptake around active neurons Most common Not motile Play a role in guiding axons to target cells during development gilial Involved in NT removal around active synapses scaffold Part of blood brain barrier btwn blood and CSF Neuron to Astrocyte Communication and Nutrient Delivery Organization of glial cell processes and neuronal dendrites and axons allow astrocytes to regulate vascular blood flow and nutrient delivery based on neuronal activity Astrocyte to Neuron Communication Astrocytes can sense and respond to nearby neuronal activity they possess They also release neurotransmitters particularly extracellular ATP enabling receptors for neurotransmitters neuron glia neuron crosstalk o In the presence of activity the glial cells release ATP So does this mean that glia can be part of the information processing capacity of the brain See picture 2 C Microglial cells Found in the cerebrospinal fluid and CNS small motile phagocytic cells like macrophages can engulf particles following injury Can secrete signaling molecules that modulate inflammatory response to injury e g cytokines Mobilized after damage become active and invade areas after damage Oligodendrocytes responsible for myelination in the CNS Schwann cells form the myelin sheath around axons in the peripheral nervous system PNS Glial cell types cont Glial stem cells Undifferentiated Glial Stem cells in the brain and elsewhere can proliferate and differentiate into new glial cells and in a VERY FEW places in the brain into new neurons A sub class of glial stem cells oligodendrocyte precursor cells primarily differentiate into new oligondendrocytes Cellular anatomy of the Nervous System The NS is constructed of neurons and glia Sounds simple but Because of the structural diversity of neurons and glia any one part of the NS contains a bewildering array of anatomically distinct neuronal types However parts of a NS are often composed of multiple layers of cells which simplify things a bit Each layer contains a limited sub set of neuronal types which interact to create mutiple parallel copies of a simple local circuit designed to perform a single computational task Cytological stains for neurons Nissel stains labels ER in neuronal cell bodies often shows up the division of parts of the CNS into layers due to differing cell density in each layer o Good for distinguishing tissues and layers within the NS but does not distinguish individual neuronal types well because it does not stain the axons and dendrite patterns Golgi stain randomly stains a few whole individual cells in a tissue entirely shows axon dendritic branching Injection into cytoplasm or application onto membrane surface of fluorescent dyes stains the whole of a particular cell useful after recording electrically from the cell through an intracellular micropipette Water soluble dyes used for injection into a neurons cytoplasm most cannot exit that cell o lipid soluble dyes placed on a neuron s membrane most cannot leave that cell s membrane Other Methods for labeling and staining neurons to show their structure and to distinguish different neuronal types Antibody labeling of proteins expressed only by a specific neuronal type Retrograde or orthograde transport of radiolabeled amino acids or fluorescent dyes along axons tracing of pathways of axons through the brain Neurons as functional units synapses to other neurons Electrical information generally flows from dendrites to axon and then via Electrical information flowing along