Semester 1 Neuroscience Flashcards

1
Q

What are the 2 areas of the nervous system?

A

Central Nervous System (CNS)

Peripheral Nervous System (PNS)

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2
Q

What do the 2 areas of the nervous system compose? (higher order organisms)

A

CNS:
- Brain and spinal cord
- Control centre for information processing and responding to sensory information

PNS:
- Cranial nerves
- Spinal nerves
- Ganglia (Dorsal root ganglia and autonomic ganglia)

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3
Q

What is a neuron?

A

It is the basic building block of the nervous system

  • Receives stimuli
  • Transmits nerve impulses or action potentials
  • Activates muscles

Neurons in all species are the functional units of the nervous system, organised into a function network capable of:

  • Response to stimuli
  • Information processing
  • Communication
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4
Q

Basic neuron structure?

A

Dendrites (located on cell body)
- Collect electrical signals and carry input to cell body

Cell body
- Integrates signals and generates an action potential

Axon
- Transmits signals over long distances from the cell body to the axon terminals

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5
Q

What is a neuronal network?

A

A series of neurons communicating with each other

Communication happens at the axons

Axon of one neuron will communicate with dendrite of other neurons

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6
Q

What is the differences in nervous systems caused by?

A

Differences amongst species are not due to the neurons, but due to how they are organised.

Also due to how well they propagate signals.

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7
Q

What organisms do not have a nervous system?

A

Sea sponges:
- Multicellular organism without a nervous system

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8
Q

What are invertebrate nervous systems specialised for?

A

They are specialised for:

  • Stimulus/response
  • Receptor/effector
  • Reflexes
  • Conditioned response
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9
Q

What are nerve nets and what is their structure ?

A

Simplest form of nervous system found in some invertebrates (hydras, jellyfish, etc)

Individual nerve cells exist in a net-like formation scattered in layers of body wall

Neurones exist in a loose network to allow for contraction and expansion of the body cavity

Nerve nets lack distinct central of peripheral regions, and anything that resembles a brain

Nerve nets have no associate activity, just reflexes (with action potentials)

However, neurones carry:

  • Information from sensory organs that detect light, touch, or other changes from the environment
  • These neurones in turn contact neurones that control movement of the organism, such as swimming

Nerve signals in a nerve net can travel in both directions

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10
Q

What is a nerve net?

A

Simplest form of nervous system in invertebrates like hydras and jellyfish

Consists of individual nerve cells in a net-like formation scattered in body wall layers

Found in invertebrates like hydras and jellyfish

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11
Q

Describe the structure and limitations of nerve nets.

A

Neurones are in a loose network, allowing body cavity contraction and expansion

Lacks distinct central or peripheral regions and anything resembling a brain

Only possesses reflexes with action potentials, no associative activity

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12
Q

How do nerve nets function in response to stimuli?

A

Neurones carry information from sensory organs detecting light, touch, or environmental changes

These neurones contact others controlling movement, like swimming

Nerve signals in nerve nets can travel in both directions

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13
Q

Which invertebrate species shows centralisation of the nervous system?

A

Sea stars display some centralisation of the nervous system

A ring of neurones is located in the centre with simple bundles of neurones (radial nerves) extending from the ring to the tip of each arm

Radial nerves form nerve nets permitting coordinated movement of each arm and the tube feet located on the surface of the arm

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14
Q

What is cephalisation and formation of the primitive brain?

A

In animals with bilateral symmetry, there is a clustering of neurones into ‘ganglia’ near the head of the animal to form a more complex system to integrate incoming/outgoing signals (seeing, hearing, tasting)

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15
Q

What is special about animals with bilateral symmetry?

A

With bilateral symmetry, 2 nerve cords run down the length of the body

This system allows more complex control of muscles for movement

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16
Q

Structure of cephalopods nervous system?

A

Cephalopods are invertebrates however display distinct CNS and PNS

Connections are required between PNS and CNS, but PNS can act autonomously in some cases

Invertebrates lack myelin but action potential propagation overcome by increasing diameter of axons

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17
Q

What do all vertebrate nervous systems contain?

A
  • Sophisticated sensory mechanisms
  • Clear differentiation of the CNS and PNS as well as sensory and motor nerves
  • Elaboration of brain structure

All contain:
- Forebrain (cerebrum, optic structures, olfactory lobe)
- Midbrain
- Hindbrain (brainstem (pons, medulla) cerebellum)

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18
Q

What is the sulci?

A

Infoldings of the cerebral hemispheres that form ‘valleys’ between the gyri

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19
Q

What is the gyri?

A

Ridges of the infolded cerebral cortex

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20
Q

What are the lobes of the human brain?

A
  • Frontal lobe
  • Parietal lobe
  • Occipital lobe
  • Temporal lobe
  • Limbic lobe
  • Corpus callosum
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21
Q

What are the two subdivisions of the PNS?

A

Afferent Sensory Division
- Information coming into the body and CNS

Efferent Motor Divison
- Information from the CNS to muscles, glands, etc…

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22
Q

What are the two subdivisions of the Efferent Motor Division of the PNS?

A

Visceral/Autonomic Motor Division
- Autonomic Nervous System, Parasympathetic and Sympathetic

Somatic Motor Division
- Voluntary

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23
Q

Structure of the forebrain, midbrain and hindbrain?

A

Forebrain (prosencephalon) consists of:
- Telecephalon (cerebrum)
- Diencephalon (thalamus and hypothalamus)

Midbrain (mesencephalon)

Hindbrain (rhombencephalon) consists of:
- Myelencephalon (medulla)
- Metencephalon (pons and cerebellum)

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24
Q

What are the divisons of the brain?

A

Cerebrum
Diencephalon
Brain stem
Cerebellum

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25
What are the functional regions of the brain?
Motor: - Primary motor and premotor in frontal lobe Sensory: - Primary somatosensory and somatosensory association areas in parietal lobe Vision: - Primary visual and visual association areas are in occipital lobe Auditory: - Primary auditory and auditory association areas in temporal lobe
26
What are the 7 major parts of the CNS?
BRAIN DIVISIONS: Cerebrum Diencephalon Brain Stem - Midbrain - Pons - Medulla Cerebellum Spinal Cord
27
What is white matter and grey matter?
Cell bodies of neurons reside in the gray matter. It has a pinkish/grey colour in the brain, and is a major component of the CNS Myelinated Axons reside in white matter. These axons connect different parts of the grey matter to each other Grey matter resides on the outside of the brain, white matter resides on the inside
28
What are the 3 brain planes?
Coronal Sagittal Horizontal/Axial
29
What are the directions of the head in a forward looking head
Anterior = front Posterior = back Ventral = front Dorsal = back Superior = top Inferior = bottom Rostral = head end Caudal = tail end (spinal cord)
30
What protects the CNS?
Bone: - Skull - Vertebral column Meninges Cerebrospinal fluid
31
What are meninges?
Meninges enclose the brain and spinal cord and their blood vessels They are formed from 3 protective tissue layers: - dura: superficial most and strongest, usually in contact with bone - Arachnoid: adhered closely to dura, web-like in appearance - Pia: deepest layer, in direct contact with CNS tissue
32
What is cerebrospinal fluid? (CSF)
It is a clear, cell free fluid produced by the choroid plexus (ependymal cells) that circulate in the subarachnoid space (the space between the arachnoid and pia mater)
33
How do the cerebral hemispheres receive input?
Afferent input goes into the somatosensory cortex (located in the neocortex, more specifically in the parietal lobe) and comes from a variety of areas: - Large portion is ascending information from the thalamus - Ascending information from the brainstem and other parts of the forebrain, also the hypothalamus - Axons travelling between hemispheres (commissural fibres) - Information from the ipsilateral cortex
34
How do the cerebral hemispheres give output?
Output from the neocortex is always excitatory from pyramidal cells (uses excitatory neurotransmitters such as glutamate, etc) - All parts of cortex project to thalamus - Axons from motor & somatosensory cortices project to basal ganglia - Axons project to brainstem (nuclei) and spinal cord - Axons project to contralateral hemisphere; axons project to ipsilateral hemisphere
35
What is the brains stems function?
Serves as a conduit for ascending & descending tracts connecting the spinal cord to higher centres (cerebrum, cerebellum) Contains important reflex centres associated with control of respiration, heart rate & blood pressure, and consciousness Contains cranial nerve nuclei
36
What are the functions of the cerebellum?
- Integrates ascending (proprioceptive) information, feeds back to cerebral cortex to refine movement - Modifies movement (compares sensory information with pre-motor information) Maintenance of upright posture Maintenance of the tension or firmness (i.e., tone) of the muscle. Aids the cerebral cortex in planning sequential movements to make smooth progressions from one movement to the next Synergy of Movement – Motor coordination Balance
37
What routes does cerebellar input come from?
- Spinal cord - Cerebellar cortex - Vestibular system - Motor systems in neocortex
38
What routes does cerebellar output take?
- Vestibular systems - Brain stem - Muscle spindles - Motor and pre-motor cortices
39
What is the spinal cord?
It is a two-way impulse conduction pathway and reflex centre It contains 31 pairs of spinal nerves in total: - 8 cervical nerves (C1 – C8) - 12 thoracic nerves (T1 – T12) - 5 lumbar (L1 – L5) - 5 sacral (S1 –S5) - 1 coccygeal (Co) These nerves give rise to the peripheral nerves of the body
40
Spinal nerve afferent information route
Each spinal nerve has a: - Dorsal root (posterior) through which afferent fibres enter, and which contains the dorsal root ganglion* (DRG) with the cell bodies of the afferent fibres
41
Spinal nerve efferent information route
Each spinal nerve has a: - Ventral (anterior) root through which the efferent fibres leave. Their cell bodies are within the spinal cord
42
What are reflexes?
Survival mechanism Inherited (‘hard-wired’), pre-set behaviour that does not require learning, practice, or experience Simplest type of animal behaviour Performed without conscious thought; usually rapid, automatic/ involuntary responses to stimuli. Usually follow specific pattern
43
What is a reflex arc and what is the structure?
The nerve pathway involved in a reflex action, including at its simplest a sensory nerve and a motor nerve with a synapse between Reflex arc structure = - Receptor (site of stimulus) - Sensory neuron (transmits stimulus) - Integration centre (can be mono or polysynaptic) - Motor neuron (conducts impulse to effector) - Effector (muscle or gland)
44
What are polysynaptic reflexes?
Reflex that involves multiple synapses between sensory axons, interneurons, and motor neurons Interneurons control more than 1 muscle group Produce either EPSPs or IPSPs Example: withdrawal reflex from hot pan
45
What is the autonomic nervous system?
The autonomic nervous system is a component of the peripheral nervous system that regulates involuntary physiologic processes including heart rate, blood pressure, respiration, digestion, and sexual arousal Contains 2 divisions responsible for the maintenance of homeostasis Both systems are continuously active under normal conditions, with each having discreet and independent functions (antagonistic functions!) ANS together with the endocrine system controls the body's internal organs, thus controlling the circulation of blood, activity of the gastrointestinal tract and body temperature. Innervates smooth muscle, cardiac muscle and glands of internal organs (Involuntary!)
46
Neuronal structure and signal summation?
Dendrites receive information from adjacent axons Axons send information from one end of the neuron to other (faster if myelinated) Oligodendrocytes provide myelination in the CNS and Schwann cells provide myelination in the PNS Signals from the cell soma are summated at the axon hillock. The hillock is considered the ‘trigger zone’ which must reach threshold potential to achieve an action potential Both the hillock and axon initial segment (AIS) are rich in voltage-gated Na+ channels. Myelin begins after the AIS
47
What proteins can be used to identify dendrites and axons in a neuron?
MAP2 (Microtubule Associated Protein) is a neuron-specific cytoskeletal protein found in dendrites Beta-IV Spectrin is a cytoskeletal protein found in axons as well as some non-neuronal cells
48
What are the 3 types of neurons?
3 types of neurons: -Motor neurons - Relay commands from brain and spinal cord to muscles and glands -Sensory neurons - Transmit information from sensory receptors to the brain and spinal cord -Interneurons - Process and integrate information within the brain and spinal cord, facilitating communication between sensory and motor neurons
49
What is golgi stain?
Golgi stain: - Nervous tissue treated with potassium dichromate and silver nitrate results in silver precipitation (from silver chromate) inside the neurons Allows us to see details of dendrites such as dendrite spines
50
What is nissl substance and how is it visualised?
Nissl bodies (or Nissl substance) are large granular structures found within neurons They consist mainly of rough endoplasmic reticulum and polyribosomes, making them key sites for protein synthesis within the neuron The presence of Nissl substance can be visualized using Nissl staining, which targets these regions specifically. Dendrites have a small amount of nissl substance Axons have no nissl substance as no protein synthesis occurs here
51
What are the 2 types of sensory neurons?
Pseudounipolar neuron 1 branch (dendritic becomes axonal) (commonly found in dorsal route ganglia) Bipolar neuron 2 branches (separate dendritic and axonal branches) (commonly found in olfactory system)
52
Spinal ganglia structure?
Ganglia are aggregations of nerve cells (ganglion cells) outside of the CNS Dorsal root ganglia are surrounded by a connective tissue capsule, which is continuous with the peripheral nerve Individual ganglion cells are surrounded by a layer of flattened satellite (fibroblast) cells.
53
What are satellite cells?
Located in the Peripheral Nervous System (PNS) Encircle and closely envelop neuron cell bodies in ganglia Provide structural support, regulate the microenvironment around the neuron, and potentially play a role in neuronal homeostasis and repair
54
What are interneurons?
Location: Primarily within the Central Nervous System (CNS) Description: Neurons that connect and relay signals between sensory neurons and motor neurons Function: Process, integrate, and modulate information within neural pathways, contributing to reflexes, relaying information, and complex processing tasks
55
What are pyramidal neurones?
- Located in the cerebral cortex and hippocampus - Large, pyramid-shaped cell body with a single, long apical dendrite and several basal dendrites - Principal excitatory neurons in the cortex, involved in motor control and cognitive functions.
56
What are purkinje cells?
- Located in the cerebellar cortex. - Large, elaborately branching dendritic tree - Principal neurons of the cerebellar cortex, inhibitory output to the deep cerebellar nuclei, playing a critical role in motor coordination
57
What are the layers of the cerebral cortex and what cells are contained within them?
Cerebral cortex is composed of grey matter Six Layers of the Cerebral Cortex: Layer I (Molecular Layer): - Contains very few neurons; mainly consists of the apical dendrites of pyramidal cells and axons from other layers. Layer II (External Granular Layer): - Similar to layer I Layer III (External Pyramidal Layer): - Contains small-sized pyramidal neurons Layer IV (Internal Granular Layer): - Mainly consists of granular cells Layer V (Internal Pyramidal Layer): - Contains large pyramidal neurons - Gives us motor output the drives voluntary muscular movement Layer VI (Polymorphic or Multiform Layer):
58
Cytoarchitecture of the cerebellar cortex?
- Three layers within the grey matter with a variety of cell types - Myelinated fibres in the white matter (deep to gray matter) 3 layers are: - Outer Molecular layer - Single layer of Purkinje cells - Granular cell layer
59
What are the three layers of the cerebellar cortex?
Molecular layer (outermost layer): - Basket cells, - Stellate cells Purkinje Layer: - Purkinje cells Granule cell layer (innermost layer): - Granule cells (most abundant neuron in brain) - Golgi cells
60
Purkinje cells in the cerebellum
- Purkinje neurons are the largest cell in the cerebellum - They have pear-shaped cell bodies and a distinctive dendritic tree (in the molecular layer) - They receive afferent information - Granule cells are the smallest in the cerebellum
61
What are neuroglial cells?
CNS: - Astrocytes - Oligodendrocytes - Ependymal cells - Microglia PNS: - Schwann cells - Satellite cells Oligodendrocytes and Schwann cells form myelin sheaths around axons
62
What do astrocytes do, what are the types of astrocytes, and where are they located?
Provide structural and metabolic support for neurons Types: - Fibrous (in white matter) - Protoplasmic (in grey matter) - Müller glia (in retina) - Radial glia (specialised cells in developing CNS)
63
What is the blood brain barrier?
A barrier composed of endothelial cells joined by tight junctions Forms glial-limiting membrane around blood vessels and along CNS surface (as part of the blood brain barrier) Prevents diffusion of solutes and fluid into brain and spinal cord O2, CO2, lipid soluble molecules (hormones) > 500 daltons MW not permissible Integrity highly dependent on astrocyte ‘end feet’
64
What are microglia?
Immune cells in the CNS Serve an immune function within the CNS much like macrophages, able to phagocytose cell debris in response to injury Normally exist as ‘resident microglia’ but become ‘activated’ upon CNS damage and actively move towards sites of injury Release cytokines which can both help and hinder recovery
65
What are oligodendorcytes?
Form myelin sheath around CNS axons, with one oligodendrocyte able to myelinate several axons Diseases that affect oligodendrocytes include multiple sclerosis and leukodystrophies One of the last cell types to form during development
66
What are Schwann cells?
Form myelin sheath around PNS axons, with one Schwann cell able to myelinate one axons Plays key role in organisation of connective tissue sheaths around peripheral nerves during development and regeneration
67
Oligodendrocytes vs Schwann cells myelination
Oligodendrocytes - Extends its projections to an axon to form the myelin - 1 cell myelinates many axons Schwann cells - Cell body engulfs axon to form myelin - 1 cell myelinates 1 axon
68
Are all axons myelinated?
No. Not all axons require myelination PNS: - Schwann cells ‘envelope’ unmyelinated axons contacting 1 or more axons CNS: - Unmyelinated axons are not associated with glial cells - Unmyelinated axons have ‘continuous conduction’ of action potentials due to passive current flow (low conduction) Examples of unmyelinated axons are: - Sensory fibres carrying pain - Temperature - Itch
69
What are some properties of neurones?
Excitability Integration/filtering & propogation of signals Transmission of signals Plasticity
70
What is the difference in ion concentration between the inside and outside of the axon?
71
How does potassium move from the inside of the axon to the outside?
It moves via potassium leak channels from an area of high concentration to an area of low concentration
72
How are concentration gradients maintained?
Ion pumps maintain the gradients, pumping ions against the concentration gradient Na+/K+ ATPase: - 3 Sodium out - 2 Potassium in - Electrogenic (blocked by ouabain)
73
What happens when permeability changes?
Sodium ions will enter (inwards sodium current) (depolarisation) Potassium ions will leave (through potassium leak channels)
74
What is the nernst equation and what is it used for?
Comparing two gradients To determine the direction of ion movement at any given membrane potential In effect, this converts chemical gradient to an electrical gradient
75
What version of the Nernst equation will we use?
at 37 degrees (for mammalian neurone) For an invertebrate, squid rt/zf is 58
76
What is the goldman constant field equation?
Essentially an extended version of the nernst equation P represents the permeability of its related ion
77
What is the ionic basis of the action potential?
Voltage gated sodium channels open Sodium enters, depolarisation occurs Action potential approaches equilibrium potential Sodium channels undergoes inactivation Potassium channels open (delayed rectifier potassium channels) Enters refractory period
78
How do voltage gated sodium channels work?
79
Diagram of action potential sequence
80
Neuronal development terminology
Neurogenesis: - Neurons are born Migration: - Neurons find their place and build e.g. cortex Differentiation: - Determination of cell fate Target innervation: - Address selection Synapse formation: - Formation of connections
81
What are the 3 layers of an embryo?
Endoderm, mesoderm and ectoderm
82
What happens at the start of neurogenesis?
At 18 days of development, after formation of endoderm, mesoderm and ectoderm, the formation of the notochord at the midline occurs The notochord instructs the development of the neural plate, which develops from overlying ectoderm (neuroectoderm) Neural plate contains a lot of cells called 'Neuroectodermal precursor cells', which play an important role in neurolation This will give rise to the entire nervous system
83
Formation of the neural groove?
As the neural plate differentiates, it folds inwards and begins to create a neural groove At the top of the groove, a neural crest begins to form
84
Formation of the neural tube
The neural plate continues to fold, and the neural folds at the top are fused together generating a neural tube Some cells from the tube migrate to form neural crest Neural crest gives rise to sensory nervous system Floorplate is located above notochord Where the tube has closed, is called the roofplate
85
What are transient structures in neurolation?
These are temporary structures that play vital roles during the early development of the nervous system Notochord: - A rod-shaped structure that forms the primitive axial skeleton. - It releases signals that influence the development of surrounding tissues, particularly the neural tube Floorplate: - Located on the ventral (front) side of the developing neural tube - It's involved in the ventral patterning of the neural tube and influences the differentiation of motor neurons Roofplate: - Situated on the dorsal (back) side of the neural tube - It's involved in the dorsal patterning of the neural tube and influences the development of sensory neurons Somites: - Secrete morphagens
86
Where does the brain and spinal chord develop out from?
Anterior End of the Neural Tube: - This part will develop into the brain. Neural Tube Near Somites: - This segment gives rise to the spinal cord - Somites are blocks of mesoderm located on either side of the neural tube and give rise to skeletal muscle, vertebrae, and dermis
87
What are neural crests?
The neural crest is a group of cells that detach from the edges of the neural tube as it closes. These cells migrate to various parts of the embryo and differentiate into a wide variety of cell types Neural crest cells contribute to many parts of the PNS, including sensory nerve cells, Schwann cells, and the autonomic nervous system
88
What happens to the lumen of the neural tube?
As the neural tube develops, its central cavity will expand and differentiate into the ventricular system of the brain and the central canal of the spinal cord These ventricles will later be filled with cerebrospinal fluid (CSF), which protects the brain, provides nutrients, and removes waste
89
What is patterning of the neuronal tube?
The neural tube is the precursor to the central nervous system (CNS), and its development is characterised by a high degree of organisation and specialisation This involves the arrangement of cells in specific patterns, both along the length and across the width of the tube
90
What are morphagens?
Neuronal tube patterning is instructed by morphagens Add. info: - Morphogens are signaling molecules that spread from specific regions in the developing embryo and create concentration gradients - These gradients provide spatial information, instructing cells to adopt different fates based on their location
91
What are the 3 primary segments that the neuronal tube becomes?
Cell division and organisation within the neural tube lead to the formation of distinct segments and regions: As the neural tube develops along the anterior-posterior axis, it differentiates into three primary vesicles or initial divisions: Forebrain (Prosencephalon): - The most anterior vesicle, which will later differentiate into the cerebral hemispheres and other structures. Midbrain (Mesencephalon): - Lies between the forebrain and hindbrain and will give rise to structures like the tectum and tegmentum. Brainstem (or Hindbrain, Rhombencephalon): - The most posterior vesicle, which will further specialise into the pons, medulla, and cerebellum.
92
What distinguishes humans from other animals?
The large size of the cortex, particularly the frontal lobe, distinguishes us from other animals
93
Time and location of birth of a neurone determines?
Timing of Birth: - Neurons born at different times often have different fates. For instance, during the development of the cerebral cortex, neurons generated early populate the inner layers, while those generated later occupy the outer layers. Location of Birth: - The region of the neural tube or neuroepithelium where a neuron is born can dictate its fate. For example, neurons born in the ventral part of the spinal cord typically become motor neurons, whereas those born dorsally become sensory interneurons.
94
Role of Morphogen Gradients in Neuronal Differentiation?
Morphogens: - These are signaling molecules that form concentration gradients in developing tissues. The concentration of a morphogen at a particular location can determine the fate of the cells in that region Morphogens will be at a higher concentration at the location they were secreted from, the concentration will drop the further away from the source of secretion The type of neurone generated depends on both the time and location of that neurones generation Morphagen gradients drive differentiation
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How do morphagens work?
Morphogens bind to receptors and set off a signalling transduction cascade that leads to activation or repression of transcription factors Transcription factors control programmes of gene expression The gene expression profile determines the cell identity
96
What determines the response of each cell embryology?
Distance from the secreting cell Availability of ligand Presence of receptors
97
What are hox genes?
Family of transcription factors Establish segmentation along anterior- posterior axis
98
How do we know that cell fate can be induced?
“Spemann-Mangold organiser” (1923, Nobel prize for Hans Spemann in 1935) Graft of tissue from pigmented to non-pigmented amphibian embryo Secondary axis developed, mixed origin Transplanted cells instructed host cells!
99
What are some names of morphagens?
Sonic Hedgehog (SHH) Bone Morphogenetic Proteins (BMPs) Wnts Decapentaplegic (Dpp) Fibroblast Growth Factors (FGFs)
100
What happens with lack of Shh? (morphagen)
Optic vesicles generated on dorsal side Shh inhibition/loss leads to loss of ventral identity Leads to synophthalmia (cyclopia)
101
What are the primary components and processes involved in building the cortex through differentiation and migration?
Neuroepithelium/Neuroepithelial Progenitor Cells: - Found in the neural tube, these are neural precursor cells that play a vital role in the development of neural tissues Ventricular Zone: - Formed by these progenitor cells, it's the innermost layer of the neural tube and a key site for cell division Radial Glia: - Cells connecting the ventricular and pial surfaces. They divide slowly and symmetrically, but can also divide asymmetrically Cell Division in Ventricular Zone: - Radial glia divide asymmetrically here, leading to the formation of "transit amplifying cells" which in turn generate new progenitors and postmitotic neuroblasts
102
What are the key steps and outcomes of neuroblast migration in cortex formation?
Neuroblasts migrate towards the pial surface Here, they form the marginal zone These migrating cells differentiate into neurons Newer neuroblasts migrate past older ones, meaning the cortex is built in an "inside out" fashion A neuron's final position in the cortex indicates its birthdate This leads to a columnar organisation of the cortex
103
What do neuroblasts become?
Neuroblasts are precursor cells that ultimately differentiate into neurons During neural development, neuroblasts arise from neural progenitor or radial glial cells Following their formation, neuroblasts undergo a migratory phase where they travel to their final destinations within the nervous system Upon reaching these destinations, neuroblasts differentiate and mature into neurons, establishing connections with other neurons and integrating into neural circuits
104
What are radial glial cells?
Cells connecting the ventricular and pial surfaces Radial glial cells serve as neural stem cells during early brain development They can divide to produce neurons directly or give rise to intermediate progenitors that then produce neurons As brain development progresses, radial glial cells can differentiate into various other cell types, including astrocytes and ependymal cells Radial glial cells can undergo asymmetric cell division in the ventricular zone. During this division, one daughter cell retains its radial glial identity and remains in the VZ, while the other can differentiate into a neuron or an intermediate progenitor cell
105
What is the origin of glia?
Also generated from neuroepithelium Over time, glioblasts either remain attached to lumen and become ependymal cells (production of CSF) Or they move to the marginal layer and form astrocytes (maintenance and repair) or oligodendrocytes (myelination)
106
What is the origin of cortical interneurons in the central nervous system?
Cortical interneurons primarily originate from the ganglionic eminences in the developing brain These precursor cells migrate tangentially from these eminences to reach the developing cortex
107
How does a growing process navigate through the embryonic body?
Growing processes use cues/ signals to help them navigate from “stepping stone” to “stepping stone" They also “piggy back” along the way, Called fasciculation
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What are guidance signals?
Guidance signals effectively guide growing processes in the embryo Can be attractive or repulsive Can be short-range or long-range Interpreted by growth cone (tip of the growing axon) that responds accordingly Acts via concentration gradients
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What are the two types of guidance signals?
Can be “non-diffusible”: - Short range - Substrate derived (ECM) - Presented on target cells (cadherins, ephrins) Can be diffusible: - Can act as gradients - Long range (netrin, semaphorins)
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What are the names of some guidance signals?
Cadherins Ephrins Netrin Semaphorins
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How do axons navigate
Axons navigate via intermediate targets Axons grow along other axons as guides
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How do we know about guidance signals?
Identified using explant, cell culture experiments, and genetic studies
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What are growth cones?
Described by Cajal, 1890 as motile structure At the tip of growing axons and dendrites Hand-like structures with receptors on the surface Senses guidance cues
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Guidance cues direct axon pathfinding by...
Binding to receptors Signalling to the cytoskeleton Acting in gradients
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Overview of axon innervation during development
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Axon guidance summary
Developing neurons are guided to their targets by attractive and repulsive cues Guidance signals act on growth cone to determine direction of growth Upon receipt of signal growth cone undergoes (actin) cytoskeletal changes to move forward or change direction Once direction determined, (microtubular) cytoskeletal changes enable laying down of axon in desired direction Targets are found and circuits formed
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What happens when growth cones reach the target?
Neurones make a number of connections with target cells Initially, surplus connections are made Connections are then refined, so the neurone innervates the correct number of target cells and the target cells are innervated by the correct number of neurones
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How is a stable synapse formed after growth cone innervation at target cell
Adhesion molecules of the pre synaptic and post synaptic sides can recognise each other Once a presynaptic axon comes in close enough proximity of a postsynaptic site where it recognises a transmembrane receptor, a connection begins to form to stabilise the transient interaction Begins to form pre and post synaptic sites Adhesion molecules: Presynaptic neurexins: - Organise the synaptic vesicle docking zone Postsynaptic neuroexins: - Recruit scaffolding proteins that recruit neurotransmitter receptorsW
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Are all contacts between axons and target kept?
Some synapses are kept, other abandoned Neurotrophins and electrical activity determine final pattern of contacts
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What is developmental cell death?
Victor Hamburger discovered that limb removal results in reduced numbers of motor and sensory neurons in the chick spinal cord (1934)
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Once circuits are formed what regulates them?
The target – continued release of trophic factors; activity Learning and memory Disease
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Brain Complexity Statistics
30,000 genes 100, 000 proteins 86 billion neurons 10-100 trillion synapses Operate responses and signals on micro-millisecond time scale. Retain or forget information for 10 secs to 70 years. It is a non vital organ as you are brain dead and survive. You can lack brain activity develop relatively normally. Underlies number of major diseases Alzheimer’s, Autism, Depression and Epilepsy
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What are some of the tools used for investigating and understanding molecular Neuroscience
DNA: - Promoter studies - Identifying mouse mutants - Disease forming mutations in humans RNA: - cDNAs - PCR - In-situ hybridization - Gene profiling (microarrays, RNAseq) Proteins: - Antibody staining (western blotting or immunocytochemistry)
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Central dogma nerve regulation
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What is glutamate and GABA?
Glutamate is the major excitatory neurotransmitter in the brain Glutamate is a naturally occurring amino acid Glutamate is an excitatory amino acid GABA is the major inhibitory neurotransmitter in the brain GABA is synthesised GABA is an inhibitory amino acid
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How is GABA synthesised?
Glutamate + Glutamic Acid Decarboxylase (GAD) ----> GABA GAD gene is recognised by transcription factors to ensure gene is selectively expressed in GABA neurons GABA is the same structure as Glutamate minus 1 carboxyl group
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What does GABA stand for?
Gamma-aminobutyric acid
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How is fine regulation achieved in neurotransmitter phenotype conversion?
Fine regulation involves a single enzyme, transcribed as a gene, regulated by DNA elements. The core pathway includes a promoter recruiting RNA polymerase for gene transcription, crucial for controlling the composition of genes expressed in neurons.
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What are the two types of elements involved in gene regulation, and how do they function?
Enhancers, located distal to the promoter, facilitate gene transcription. Silencers, on the other hand, negatively regulate expression in a time-dependent manner. This transcriptional cross talk is essential for precise control over neurotransmitter composition in neurons, exemplified by converting excitatory (glutamate) to inhibitory (GABA) neurotransmitters.
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How do neurones retain shape?
Retain this shape basic polarity static view but actually they are highly dynamic Shape is dependant on cytoskeleton
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Cytoskeletal elements compared?
Microtubules: - 25nm diameter - Made up of Alpha / Beta dimer subunits that build hollow tube - Both subunits capable of binding GTP and GDP - Microtubule has a negative (-) end and a positive (+) end Actin filaments: - 7nm diameter - G-actin monomers make F-actin filaments Intermediate filaments: -10nm diameter - Least dynamic - Dimer, with a head and tail and a twisted helical structure in-between
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Organization of the major cytoskeleton components within neurones
Actin cytoskeleton often associated in a cortical network enriched in terminal regions Microtubules orientated unidirectionally in the axon compartment but bi-directionally in the dendrite. These make tracks for transport. Neurofilament stabilizes axons Polarity in axon is negative to positive (uni-directional) Polarity in dendrites is both negative to positive and positive to negative (bi-directional)
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What are microtubule associated protiens?
They are proteins that facilitate the structure of the major cytoskeletal component of neurones, microtubules Microtubule associated protein-2 is usually associated with dendrites Tau often associated with axons
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What do kinesin and other motor proteins do?
Binds to Cargo or protein that needs to be transported Binds to Microtubules Uses ATP activity Walk along the microtubule Move protein to extremities of the processes where the major signalling happens Kinesins move towards positive end Dyneins move towards negative end
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What are the Electrical and chemical potentials that make neurons excitable?
Na+/K+ATPase pumps 3 sodiums out 2 potassiums into neurons More sodium outside (142 mM) than inside (10mM) More potassium inside (140mM) than outside (4mM) Major negative ion chloride is higher outside (103mM) inside (4mM) Minor ion Calcium outside (2mM) very low inside (100 nM).
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How do neurones communicate?
Processes with polarity (axon and dendrite) Come close to each-other, potential to communicate Using electrical communication to allow intercellular communication Using chemical communication to allow intercellular communication
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Sodium channel structure?
Sodium Channels made up of one protein sequence that contains 4 domains. Each domain has a voltage sensor and ¼ of the pore. Each domain is linked via intracellular loops Each domain is made of 6 transmembrane helices Intervening between #5 and #6 is a sequence called a re-enterant loop Threshold for activation about -50 mV Threshold for inactivation about 0 mv Selective for Na+
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Potassium channel structure?
Potassium Channels made up of one protein sequence that contains 1 domain. Each domain has a voltage sensor and ¼ of the pore. Come together in a tetramer to make a functional channel. Threshold for activation about 0 mv Threshold for inactivation +50 mV Selective for K+
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What are the two ways of bridging the synaptic gap?
Electrical Synapse - Signal passed direct electrical flow between two cells Chemical Synapse. - Electrical signal converted to a chemical signal and then back into an electrical signal
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Chemical synaptic transmission
Stimulated neuron opens ion channels including those that allow Ca2+ into nerve terminal. Ca2+ is sensed. Recognized by a protein that binds Ca2+ and changes its conformation. (Synaptotagmin). Change in conformation allows proteins SNARE proteins to promote fusion via a vesicle/plasmamembrane protein complex. Vesicle fuses with the plasma membrane, NT released and diffuses into the synaptic cleft. Receptors bind NT and these proteins are ion channels. NT binding opens (or is gates) receptor channel, allows ions to flow and change distribution across membrane. Excite by depolarizing the membranes {positive signal}. Inhibit by hyperpolarizing the membrane {negative signal}. Chemical signal is terminated by diffusion away or reuptake from the synaptic cleft.
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Synaptotagmin
Synaptotagmin is a vesicle protein - Has protein domains that bind Ca2+ - Changes conformation when bound Ca2+ - Allows vesicle to see the signal from Ca2+ Ca2+ bound synaptotagmin promotes vesicle SNAREs and plasmamembrane SNAREs to complex using complementary protein interaction domains (i.e. coil-coil domains) this promotes fusion.
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What are the types of synaptic sites and how do they produce inhibitory and excitatory responses in post synaptic neurones
Axo-dendritic synapse - Axon --> dendrites Axo-somatic synapse - Axon --> cell body Major excitatory synapse are on the dendrites and use glutamate as the transmitter Major inhibitory synapses are on cell body and use GABA or glycine as the transmitter
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Glutamatergic vs GABA/Glycine synapse structures
They look different and are molecularly distinct. Glutamatergic are often Asymmetric - Vesicle called vesicle glutamate transporter - Post synapse has thick specialization organizer proteins and cytoskeleton - Post synaptic receptors are glutamate specific - Flux of Na+/Ca2+ excites synapse GABA/Glycine synapses are symmetric - Vesicles called inhibitory amino acid vesicle transporter (IAAT) - Post synapse has thin specialization organizer proteins and cytoskeleton - Post synaptic receptors are glycine/GABA specific - Flux of Cl- inhibits synapse
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Key Features on excitatory and inhibitory receptors
Glutamate receptors - Four subunits to make ion channel - Glutamate binding site on outside - Cation Channel - Bind to molecules like PSD-95 on inside of postsynaptic cell. Glycine receptors (GABA recpetors) - Five Subunits to make ion channel - Glycine binding site on outside - Anion Channel - Bind to Gephyrin on the inside postsynaptic cell
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What are neurexins
Neurexins a family of presynaptic tags Neuroligin 1 is a postsynaptic glutamatergic tag Neuroligin 2 is a postsynaptic glycinergic tag
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Neuroligins and neurexins
Neurexins (presynaptic) and neuroligins (postsynaptic) interact with each other at the synapse Neuroligins interact with PSD95 (excitatory) or Gephryn (inhibitory) in the postsynaptic nerve to organise tags and receptors Selective use of molecules can define synapse - neuroligin 1, 3, 4 are excitatory - neuroligin 2 is inhibitory Make multiplex protein complex that are adhesive and bring about signalling
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molecular neuroscience disease examples
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What is Ohms Law
V = IR R = V / I