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2 What are the nervous system s functions? The nervous system organizes and controls an individual s appropriate interactions with the environment. Thus, it s functions are dynamic, vast and wideranging extending to include all thoughts, perceptions, bodily actions, behaviors, and even the very essence of one s being: consciousness and the mind.

3 We will focus on 3 basic features of the nervous system The mechanisms by which neurons produce signals. The patterns of connections between nerve cells. The relationship of different patterns of interconnections to different types of behavior. Bio 126- Advanced Neuro, Zuo, spring quarter Bio127- Mechanisms of Neurodegenerative disease, Saxton, Spring. Bio 128- Developmental Neuro, Chen, Winter.

4 The nervous system and its function is the product of both our genes and our environment We are now in a gene-centric post-genomic phase of neuroscience human genome sequenced- approximately 20,000 genes. Most genes are expressed in the brain, either during development or in the adult. It is the spatial and temporal regulation of these genes that builds a nervous system. Mice, flies, and worms have nervous systems and even express many of the same genes as humans. Genetics allows us to correlate gene activity with nervous system function. Neuroscience therefore encompasses the fields of genetics, cell biology, physiology, and development biology.

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6 Most genes expressed in the brain are not brain specific

7 A single mutation can lead to dramatic brain size defects Mutation in a spindle pole gene call ASPM1

8 It is hard to visualize and monitor neurons and manipulate genes in humans so neuroscientists study a number of different organisms. worm nervous system highlighted with green fluorescent protein (GFP): 302 cells

9 The mouse is a common model in neuroscience research

10 Squids have unusually large axons

11 Higher mammals are used to study more complicated brain functions

12 Lesions in brains or degenerative diseases help us understand brain function Phineas Gage- Railroad spike through frontal lobes changed His personality.

13 What are brains made of?

14 What are brains made of?

15 How many neurons in a human brain?

16 How many neurons in a human brain? 100 thousand 10 million 100 million 1 billion 10 billion 100 billion

17 Brains are made up of cells Camillo Golgi (Italy)- believed that cells in the brain were connected forming a continuous network (reticular theory). Santiago Ramon y Cajal (Spain)-Brains made up of single cells-communicate at specialized areas called synapses. Shared nobel prize in 1906

18 The Nobel Prize in Physiology or Medicine 1906 "in recognition of their work on the structure of the nervous system" Camillo Golgi Pavia University Pavia, Italy Santiago Ramón y Cajal Madrid University Madrid, Spain

19 Golgi staining: potassium chromate and silver nitrate (1873) Golgi's drawing of the hippocampus impregnated by his stain (from Golgi's Opera Omnia). Nobel e-museum

20 The nervous system as a diffuse reticular syncytium? (i.e. a mass of cytoplasm with many nuclei but no internal cell boundries) Camillo Golgi Nobel Lecture December 11, 1906 The Neuron Doctrine- theory and facts...far from being able to accept the idea of the individuality and independence of each nerve element, I have never had reason, up to now, to give up the concept which I have always stressed, that nerve cells, instead of working individually, act together, so that we must think that several groups of elements exercise a cumulative effect on the peripheral organs through whole bundles of fibers.

21 The Neuron Doctrine: (Santiago Ramon y Cajal) Neurons are cells. Each is an individual entity anatomically, embyologically, and functionally. Also: Neurons have a functional polarity. l

22 Two basic cell types in the nervous system Neurons and Glia

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24 Glia Outnumber neurons by fold myelin sheath. blood-brain barrier removing debris and excess neurochemicals structural support for neurons critical role in brain development.

25 Types of glial cells Microglia- phagocytes, mobilized after infection, injury, or disease Macroglia- three types Astrocytes-CNS, most numerous type of glia and contain star shaped long processes. Oligodendrocyes- Myelin producing cells of the CNS. Schwann cells-myelin producing cells of the PNS.

26 Astrocytes Restricted to CNS Maintain a proper chemical environment

27 Oligodendrocytes Myelinate axons in CNS Each cell can myelinate multiple axons

28 Schwann cells Myelinate axons in PNS One axon per cell Cross section through PNS nerve

29 Types of Glial Cells in the CNS Microglia Astrocytes Oligodendrocytes

30 Neurons Main signaling unit of the nervous system Polarized-have axons and dendrites Communicate by electricity- usually using action potentials. Tremendous range of different cell typescategorized by morphology, molecular identity and physiological activity.

31 Which of the following cell structures are found in neurons? DNA RNA Nucleus ER mitochondria microtubules Golgi Cell division machinery

32 Neurons have a functional polarity. synapses Incoming information arrives Information is assimilated Information is sent to next neuron

33 Structures of a neuron cell body (soma)-metabolic center of the cell, contains the nucleus. dendrites- receive incoming signals from other nerve cells axon- carries signals to other neurons axon hillock-initiates action potentials synapse-site at which two neurons communicate synaptic cleft-area between pre and post-synaptic cell

34 Cell Body Structure Figure 12.4

35 Neuronal Processes: Dendrites Dendrites Extensively branching from the cell body Transmit electrical signals (graded potentials) toward the cell body Function as receptive sites for other neurons

36 Purkinje cell hipocampal dendrite

37 Dendritic Spines axon spine astrocyte dendrite

38 Neuron Processes: Axons Axons (nerve fibers) Neuron has only one, but it can branch Impulse generator and conductor Transmits action potentials away from the cell body

39 Axons Neuron Processes: Axons Neurofilaments, actin microfilaments, and microtubules Provide strength along length of axon Aid in the transport of substances to and from the cell body Axonal transport

40 Neuron Processes Axons Branches along length are infrequent Axon collaterals Multiple branches at end of axon Terminal branches End in knobs called axon terminals (also called end bulbs or boutons) Neuron Structure

41 Neuron Processes: Action Potentials Nerve impulse (action potential) Neuron receives and sends signals Generated at the initial segment of the axon Conducted along the axon Releases neurotransmitters at axon terminals Neurotransmitters excite or inhibit neurons

42 Neurons are classified in different ways Morphology: unipolar, bipolar, and multipolar Function: sensory neurons, motor neurons, and interneurons Neurotransmitter expression- excitatory, inhibitory, dopaminergic, etc.

43 Some nerve cell morphologies found in the human nervous system

44 Purkinje cell cerebellum Hippocampal neuron

45 Pyramidal neurons: multipolar neurons that contain both apical and basal dendrite. Also contain 1 axon. Most common excitatory neuron in the cerebral cortex.

46 Different morphologies of neurons in the retina. Coombs et al., 2006"

47 Fluorescence Microscopy Fluorescent molecules absorb light at one wavelength and emit it at another-longer wavelength. Uses filters to allow only light of a given wavelength in and out. Can detect specific proteins or other molecules in cells and tissues. Fluorescein (emits green), rhodamine (deep red) are molecules that can be chemically coupled to proteins to detect their localization indirectly GFP, isolated from jellyfish is a protein (encoded by a gene) that has intrinsic fluorescence.

48 Secondary antibodies recognize primary antibodies and are species specific.

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50 If you want to look at a macromolecule inside a cell, but it is not fluorescent use indirect immuno-fluorescence microscopy

51 GFP is an intrinsically fluorescent protein

52 GFP can be expressed behind Specific promoters Here expressed in a fly Periferal neuron Figure 9-25 Molecular Biology of the Cell ( Garland Science 2008)

53 GFP can be used to create designer pets glowing-animal-pictures/ - /glowing-algae-petri-dish-animals_11834_600x450.jpg

54 All kinds of fluorescent protein variants these days

55 Basic structure of a sensory neuron (afferent) spinal cord skin

56 Structure of a motor neuron (efferent)

57 Neurons communicate by electricity Axons project great distances Neurons do not touch each other directly. Come in close proximity at the synapse Use action potentials to transmit information Action potential causes release of neurotransmitter that is received by post-synaptic cells.

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59 Properties of the action potential rapid transient all or none self-regenerating can go long distances. 15 m in a giraffe highly stereotyped discrimination is based on patterns of firing

60 Neural Circuits Neurons don t function in isolation- they are organized into circuits that process specific kinds of information. Direction of information flow is important for understanding the function of a circuit Afferent neurons-carry information toward the brain Efferent-carry info from the brain

61 example of a simple circuit: knee jerk response (myotatic reflex) A simple neural circuit.

62 The knee-jerk response, a simple reflex circuit

63 Ways to measure neural activity Extracellular recording- an electrode is placed near a neuron. Measures action potentials. Useful for detecting patterns of activity. Intracellular recording-an electrode is placed inside a neuron-can measure smaller graded potential changes. Useful for isolating responses to single inputs.

64 Relative Frequency of Action Potentials in Different Components of the Myotatic Reflex extracellular recordings-action potentials

65 Intracellularly Recorded Reponses Underlying the Myotatic Reflex

66 Neural Systems circuits that do the same kinds of things are grouped in systems, for example sensory systems and motor systems. Many neurons function between these systems, called associational systems, very complex and least characterized systems

67 The Major Components of the Nervous System and Their Functional Relationships

68 Cell bodies that do similar things are grouped together PNS-- Nerve cell bodies are located in ganglia (ganglia have neurons and glia in them). Dorsal root ganglia in spinal cord, cranial nerve ganglia in brainstem, etc. CNS- Nuclei are compact accumulations of neurons having roughly similar connections. Cortices (cortex) sheets of cells of similar function.

69 Cerebellum (cortex) Thalamic Nuclei

70 Other terms Nerves- bundles of axons, enveloped by glial cells that myelinate them White matter- areas of axon tracts Grey matter- areas of cell bodies

71 White and grey matter