Lecture 1/2: Introduction to Neuroscience Flashcards
Human Nervous System: CNS and PNS
Central nervous system (CNS)
◼ Brain
◼ Spinal cord
Peripheral nervous system (PNS)
◼ Sensory neurons
◼ Somatic motor division
◼ Visceral/autonomic motor division
What did Camillo Golgi discover and how?
In the Early 19th century, the cell was recognized as a fundamental unit of living organisms but they were not recognized as central to nervous tissue until 20th century. They had a hard time finding the cells in the nervous system because of the shape that the neurons are in.
Until Golgi developed a way of staining cells…
◼ Camillo Golgi discovered that by soaking a brain in silver chromate solution, a small number of cells became fully-filled with dark color. The parts that were darker than the others in the golgi stains were the neurons.
What is the neuron doctrine?
◼ Golgi supported the ‘reticular theory’ that all neurons formed a single continuously connected network. All th systems are interconnected, they are not units that are seperated from each other like the cell, but they are all interconnected. Because they couldnt see where one cell started and one finished, they thought it was all interconnected. It is all one single unit.
◼ Ramon y Cajal used Golgi’s method to reconstruct neurons and argued for the ’neuron doctrine’ that neurons communicate at specialized contact points rather than through physical continuity. “The neuron is the unit of the nervous system”.
How did they prove that the neuron doctrine was correct?
The neuron doctrine was not finalized until sherrington offered that different cells were connected by synapses. By the1950s, Ultimate proof of the neuron doctrine required development of electron microscopy (1950s) to visualize synapses and confirm that neurons are discrete entities
Who named the points of communication?
Charles Sherrington (early 1900s) identified these points of communication as ‘synapses’
What are the two basic cell types in the nervous system? What are their roles?
◼ Neurons and glia are the primary cells of the brain
Neurons
◼ Process information
◼ Sense environmental changes
◼ Communicate changes to other neurons via electrical signaling
◼ Control bodily response
Glia
◼ support the signaling functions of neurons
◼ insulate, nourish, repair neurons (but probably much more!)
◼ Glue (glia comes from greek word that means glue) = keeps neurons together.
Nerve Cell Morphologies
- Most neurons have dendrites (input of the neuron). Then information reached the cell body then passes through axon (output).
- Most have one single axon.
- How many branches they have in their dendrites can be used to determine the role they might play.
Types shown below:
B) Retinal bipolar cell: relay information. Very narrow dendrites. Does not have lots of arberrations so it is relaying information. Get info, send it and pass to next one.
C) The retinal ganglion cell: Integrate information. The arberations of the dendrites are spread out so they get a lot of information from a lot of cells. Gradually getting info and collecting it and then send it. In thiss image, you can see that the arberations are all in the same layer of the cell. Therefore, they will get the input only from that specific layer that doees a specific process.
A) Cortical Pyramidal Cell: its arberations are pasing through multiple different layers of the cell so it will get input from many different layers.
D) Retinal amacrine cell: Previously they thought it did not have an axon. It is like an interneuron. Simply passing information to another layer. Passes info from same layer of different layer.
* Important to unnderstand why there are different shapes for the cell.
Cells in the Cerebellum
Cerebellar Purkinje cells
* Important for motor learning, coordination, balance (motor memory - will never forget how to ride a bike).
* Cerebellum saves motor memories.
Dendrites
primary target for synaptic input
Primary input of the neuronss.
Axon
signal transduction from cell body; reads out information (output).
Action Potential
electrical event that carries signals. Either you have it or not
Presynaptic terminal
where molecules are secreted into synaptic
cleft. Found at the end of the axon.
Postsynaptic ternmial
contains receptors where molecules
bind
Synaptic cleft
space between pre- and post-synaptic terminals
What makes neurons special for long distance electrical signalling?
Extensive branching
Dendrites:
◼ Primary targets for synaptic inputs from axon terminals of other neurons
◼ Extensive branching that differs greatly between neuron types
◼ Complexity of dendritic arbour depends on number of inputs a neuron receives
◼ Arbour complexity dictates capacity to integrate information from many sources
◼ If dendrites have extensive branching, it means they are integrating information from a lot of different sources. If dendrite is connected to one different cell then it just does a relay of information.
Axon:
◼ Most neurons have only one that extends for a long distance
◼ Some branching
◼ Site of output to other neurons
◼Axon length varies depending on their role. Neurons that innervat our foot are the longest ones (1m).
What is an action potential?
Information conveyed by synapses on the dendrites is integrated and converted to an electrical signal, the
action potential, at the origin of the axon.
◼ Action potentials (also called ‘spikes’ or ‘units’) are ‘all or nothing’ changes in electrical potential across the neuronal cell membrane.
◼ The axon extends from the neuronal cell body and may travel a few hundred micrometers or even further
◼ e.g. local interneurons have very short axons
◼ e.g. axons from the human spinal cord to the foot
are a meter long
◼ Axons can branch to innervate multiple post-synaptic sites on multiple neurons. There are a few neurons which may innervate by one single neuron.
What is the structure of synapses and why does it allow for communication between neurons?
◼ The axon terminal of the presynaptic neuron is immediately adjacent to the postsynaptic area on the target cell
◼ Neurotransmitters are specialized molecules that are released from the presynaptic terminal, cross the
synaptic cleft, and bind receptors in the postsynaptic density.
◼ The neurotransmitters are collected by special channels on the other side of the synaptic cleft. If enough information of those is reached then the postsynaptic is going to fire an action potential and the info will be transferred to this channel.
Basic Structure of Neurons
Glia
◼Glia also have complex processes extending from their cell bodies but these serve different functions than neuronal processes
◼ Glia is Greek for ‘glue’ – long thought that glia’s primary purpose was to hold neurons together
◼ MS is an autoimmune disorder - attack myelination of neurons.
◼Glia support neurons, glia cells myelinate the neurons, nourish the neurons and speed uop the speed of neurons.
How does Saltatory Conduction work
1) A depolarizing stimulus, a synaptic potential or a receptor potential in an intact neuron or an injected current pulse in an experiment locally depolarizes the Axon, opening the voltage gated sodium channels in that region.
2)The opening of sodium channels causes inward movement of sodium and the resultant depolarization of the membrane potential generates an action potential at that site.
3)Some of the local current generated by the AP flows passively down the axon. This passive current flow depolarizes the membrane potential in the adjacent region of the Axon thus opening the sodium channels in the neighbouring membrane. The local depolarization triggers an AP in this region, which spreasds again in a continuing cycle until the end of the axon is reached.
4) The regenerative properies of sodium channel opening allow action potentials to propagate in an all or none fashion by action as a booster at each point along the Axon. Note that as the action potential spreads, the membrane potential repolarizes due to potassium chanel opening and sodium channel inactivation leaving a wake of refractoriness behind the action potential that prevents its backwards propogation.
Why does myelin improve passive flow of electrical current?
Myeling insulates the axonal membrane reducing the ability of current to leak out of the Axon and thus increasing the distance along the axon that a given local current can flow passively.
It acts as an electrical insulator and greatly speeds up action potential conduction. The major reason underlying this marked increase of speed is that the time consuming process of action potential generation occurs only at specific points along the axon called the node the Ranvier (gap in myelin). The Action potential jumps from node to node - the AP generated at one node illicits current that flows passively within the myeling until the next node is reached.
unmyelinated 0.5-10m/s
myelinated 150m/s
What increases the speed of action potential propagation?
1) myelination
2) Diameter of axon
Glia Functions
Glia serve diverse functions including:
◼ Maintaining the ionic milieu of neurons
◼ Modulating the rate of action potential propagation
◼ Modulating synaptic transmission by regulating
neurotransmitter uptake & metabolism at the synaptic cleft
◼ Regulating recovery from neural injury
◼ Interface between brain & immune system
◼ Facilitating flow of interstitial fluid through the
brain during sleep
Astrocytes
Type of glia:
◼ Restricted to brain & spinal cord (only in CNS)
◼Nourishing
◼ Major function is to maintain the appropriate chemical environment for neuronal signaling, including formation of the blood-brain barrier
◼ Recent evidence suggests astrocytes secrete
substances to influence construction of new synaptic
connections
Oligodendrocytes
Type of glia:
◼ Restricted to brain & spinal cord (CNS)
◼ Lay down myelin around axons, regulating speed of transmission of action potentials
◼ Myelinate CNS
Schwann Cells
Type of glia cell:
◼ Provide myelin in the peripheral nervous system
Microglia
Type of glia:
◼ Primarily scavenger cells that remove cellular debris from sites of injury or cell turnover
◼ Secrete signaling molecules, particularly cytokines (immune signaling molecules)
◼Immune system, clean up mess and injuries
Glial Stem Cells
◼ Cells that retain the capacity to proliferate and generate additional precursor cells or differentiated glia or neurons
◼Can produce the other types of glia cells or can produce new neurons.
Neural Circuits
◼ Neurons do not act alone. Nothing can be done my just ine neuron. A subset of neurons that come together can form neural circuits that do one single job
◼ Diverse subsets of neurons are organized into
ensembles called neural circuits that process specific
types of information. Neural circuits work together.
◼ Specific arrangement varies with function
◼ All process in transportation of information is done by neurons
Direction of flow in neural circuits
Direction of information flow defines all circuits
◼ Afferent neurons carry information toward central
nervous system (CNS).
◼ Efferent neurons carry information away from CNS.
◼ Interneurons participate in local aspects of circuit function. They are intermediates - they get information from the CNS and send their output to the CNS. role of interneurons is mostly processing info.
The knee jerk response
Extensor muscle = quad, Flexor muscle = hamstring
When you tap a hammer to your knee, your leg will kick out. In order for your leg to kick out, the quad muscle has to flex (aka get shorter) and the hamstring muscle has to do nothing (not object).
1) The sensory neuron (DRG neuron) detects the tap and sends the signal down the axon, in the form of action potentials, to the spinal cord.
2) In the spinal cord, it synapses onto two cells. One of them is the motor neuron that innervates your quad muscle (the one that has to flex) and the other one will innervate an inhibitory interneuron.
3) In both these cases, the sensory neuron will release glutamate to excite both the cells. It will cause the motor neuron to be excited and flex the quad muscle. It will also cause the interneuron to be excited and release GABA or glycine (inhibitory neurotransmitters) onto the motor neuron that innervates the hamstring muscle. Therefore, it causes a large IPSP in the motor neuron that innervates the hamstring muscle causing it to not fire.
4) The neurotransmitter that is released in the neuromuscular junction is acetylcholine (hamstring muscle)- excitatory.
extensor = activated (receives excitatory)
flexor= not activated (receives inhibitory)
Muscles are always in pairs (flexor and extensor) that always work together.
Neuron that synapses onto the hamstring is inhibitory and neuron that synapses onto quad is excitatory.
Restrictions for how fast or slow your response is:
1) speed by which info passes through axon.
2) Synapses
Neural Circuit Structure and Function
Circuit arrangement varies according to function
◼ Divergent circuits: spread information. Get info and pass it to more neurons - 1 neuron synapses to 3 neurons.
◼ Convergent circuits: integrate information
afferent = towards CNS
efferent = towards periphery
remember:
What are the methods for studying neural circuits?
1) Electrophysiological recordings
2) Calcium imaging
3) Optogenetic
Extracellular recording and the knee-jerk reflex circuit
- We do the recording at the side of the neuron itself (not inside the soma).
- Sensory neuron: you see the background activity of the neuron and then when it sends the sensory inputs, your sensory starts firing. Now you are recording the action potential. HIGHER FREQUENCY = MUSCLE is STRECTCH. The higher the frequency = stronger stretch.
- In the motor system, we have muscles that do in the direction that you intend to move = agonist muscles. Oposing muscles are called antagonist muscles. Extensor = agonist muscle and flexor = antagonist muscle.
- Motor neuron: You can see that the muscle activity is more condensed (higher frequency) which means it will contract. You can see that there is a delay between the sensation and the activity of the muscle.
- The interneuron receives the same information which are gonna sned it to the opposing muscle. It iis going to be inhibitory.
- The opposing muscle (flexor) receives the inhibitory signal and relaxes (less activity). The opposing muscles is not going to oppose the motion and your leg will extend.
- Tonic activity (background activity): we always have some tonic activity of our muscles.
Intracellular recording and the knee-jerk reflex circuit
- If you go inside the soma and record from the muscle (inside the neuron) then you can record the graded potential.
- Sensory neuron: See Action potential. Same for the motor neuron (extensor) and interneuron.
- Motor neuron (flexor): depolarizes, this is why you have less tonic activity at that neuron.
What type of studies do we use for optogenetics?
- use animal studies
- Channels are sensitive to light and so you can make them open which results in the firing of an AP as long as you have the light. When the light is shined on the neuron, they will start firing
- They can be activating (fire AP) or deactivating (inhibit AP).
- Optogenetics can help us determine which is the input and which is the output of the system.
- Striatum is the input of the basal ganglia and substantia nigra is the output. How can we establish that the direction of info is from the striatum to the substantia nigra? Is this connectivity excitatory or inhibitory?
1) They expressed genetically sensitive cells to the striatum of the mouse. So now you have neurons that fire when you shine a light to the striatum.
2) If there is no connectivity between the striatum and the substantia nigra, you expect no changes in the background activity.
3) However, there is either an increase or decrease of activity as a result of this change. This means there is a connection between the neurons of your input and output.
4) We can see that the change in firing is less than the background activity, so we know that there is a connection between the two and that the connection is inhibitory.
-
The building blocks: Neuron, Circuit
& System
- Neurons never work alone. Neurons come together and build a circuit. Each neural circuit processes one specific kind of info. And then your circuits get together and build neural systems.
- Diverse subsets of neurons constitute ensembles called neural circuits which are the primary components of neural systems that process specific types of information
Neuron Anatomy
Is the information topographically represented?
◼ Systems that distinguish differences between neighboring points (e.g. vision, in visual field or touch, on the body’s surface) represent information topographically
◼ Topographic maps reflect a point-to-point correspondence between the sensory periphery and neurons within the CNS. Different area of the body represented in a different area of the somatosensory sytems.
◼ Topographic informaion is important to know where you were touched, without this you would know you were touched but not where you were touched.
◼ Other systems (e.g. smell, taste) use computational maps to compare, assess, & integrate multiple stimulus attributes to extract essential information about stimuli. The topographical map is not very important for smell or taste - we dont have a topographic maps of information for these systems.
◼ Higher order systems (e.g. language, emotion) are less well understood and may not follow the neat organization of sensory & motor systems. It is not obvious if these regions are topography represented, they are not as well organized as the somatosensory and visual systems. .
What technique is used for genetic analysis of neural systems?
Genome wide associatio studies (GWAS)
◼Correlational studies - only gives you a guess, cannot be certain. It is observational.
◼ Large scale population studies that assesses statistical correlation between genetic variation and frequency of clinically diagnoses conditions to identify ‘risk locus’ for a particular condition.
◼ example: for alzeihmers, they have target genes that they think are responsible for the disease.
◼ After you find what genes might be responsible for the specific disease, then you need to find an animal model for that gene. Usually they will use animals that have a higher percentage of their genes expressed in their nervous system because they want find it to be as similar as humans.
- the animals that they often use that meet this criteria are: fruit flies, zebra fish, nematode c elegan, mouse.
◼ Once candidate genes have been identified in humans, these can be studied in cell models or animal models to understand the biological function of these genes. You can use the animal model to study a drug, manipulate that gene in an animal and observe to see if that animal develops the disease that you have studied in humans. If this is the case, you can now find a solution for it.
Genetic engineering
- Once you know that a specific gene might be responsible for a disease, you can manipulate that gene in an animal and try to express specific things that you think are responsible for the human disease.
- Now after 2 generations, you have an animal that has that gene that expresses the disease. The animal should show the behavioural effect of the disease.
- The animal can now help us find a solution: find a drug that helps the animal and use it to find one that helps the humans.
What strategy do we use for the structural analysis of neural systems?
◼ Tract tracing permits detailed assessment of connections between brain regions
- typically use viruses
- inject a site with either a retrograde or anterograde tracer.
◼ Retrograde: travels in the oppossite direction of the flow of information. Use a retrograde tracer when we want to know the input of that specific site - wha areas send info to this site.
◼ Anterograde: travels in he direcion of the flow of information. Here we want to know where this area sends the information = the output of the area.
◼Allows us to detect the input and outputs of a specific area during different times.
◼ You can find first order neurons (first level that they send their input to), second order neurons by changing the timing. Can determine how long (days) to reach the first level .
◼done in animals, animal usually sacrificed after
What strategy iss used for functional analysis of neural systems?
◼Historically, the most widely used methods were electrophysiological recording and functional brain imaging.
◼ Mostly done in animals unless if a human is already undergoing a surgery (dr. penfield).
◼We have receptive fields in many different places (vision, skinn). These are sensitive neurons that will fire once you touch them.
- if you touch the center, wheree the neurons are sensitive, that neuron will fire.
- if you touch the surrounding area there will be a decrease in firing frequency.
- if you touch the area not in the receptive field of the neurons, there is no change in the background firing.
Anatomical References
◼ We need directions for the 3D structure of the brain
◼ In animals that walk on all fours, the directions for body &
brain are the same
◼ Since humans walk upright, our head is at an angle to the our body
◼ Anterior, posterior, superior and inferior refer to the long axis of the body so have the same direction for forebrain and brain stem (extra-centric references have nothing to do with brain and spinal cord.
◼ Dorsal, ventral, rostral & caudal refer to the long axis of the CNS
Brain stem & spinal cord
* Dorsal is to the back
* Rostral is towards the top of the head
Forebrain
* Dorsal is toward the top of the head
* Rostral is towards the face
What are the anatomical planes?
- 3 different planes
- Sagittal
- Horizontal (axial
- Coronal (frontal)
- Sagittal
- When we cut the brain along the midline, we observe the brain has bilateral symmetry
Contralateral vs Ipsilateral
- Contralateral: on opposite sides of the midline
- Ipsilateral: on the same side of the midline
- E.g. The left visual cortex receives both ipsilateral projections from the left eye and contralateral projections from the right eye
Spinal cord
Different nerves originate from our spinal cord.
* the cervical part and lumbar part of our spinal cord have some enlargement.
* The reason for the enlargement is that not all body parts need the same representation. We use our feet and hands a lot more (we are dextrous), this is why we need a larger representation of them
* Enlargement of those two segmentss to accomodate more neurons.
Surface anatomy of the cerebral hemisphere.
Pre central gyrus = primary motor area
Post central gyrus = primary somatosensory
* The hand knob (has all the motor neurons for hand movement) is a helpful landmark to find the central sulcus in fMRI studies.
Surface Anatomy of cerebral hemisphere (2)
Spinal cord - external anatomy
◼ The peripheral nerves that innervate much of the body arise from the spinal nerves
◼ Sensory information carried by afferent axons of the spinal nerves enters the cord via the dorsal roots. Dorsal root is the one that brings the sensory info to the spinal cord.
◼ Motor commands carried by the efferent axons leave the spinal cord via the ventral roots. Ventral root is the one that will send the motor commands to the muscles.
◼ Once the dorsal and ventral roots join, sensory and motor axons usually travel together in the spinal nerves
◼So the peripheral nerve that goes to the limb basically have both sensory and motor nerve. When it reaches the spinal cord, they will go to different root: dorsal root will be sensory, ventral root will me motor.
Internal anatomy of spinal cord
◼Interior of the cord is formed by gray matter (neurons), surrounded by white matter (axons)
◼ Cervical and lumbosacral (lumbar) enlargements accommodate the greater number of nerve cells and connections required to process information from upper and lower limbs
Lateral columns, Ventral colums, dorsal horns, ventral horns
◼ Lateral columns include axons that travel from the cerebral cortex to interneurons and motor neurons in the ventral horns (‘lateral corticospinal tract’)
◼ Ventral columns carry both ascending information about pain & temperature (special sensory info), and descending motor information from the brainstem & motor cortex
◼ In transverse sections we can identify the dorsal and ventral horns in the gray matter
◼ Neurons of the dorsal horns receive sensory information that enters via the dorsal roots of spinal nerves
◼ The ventral horns contain the cell bodies of motor neurons that send axons via the ventral roots of spinal nerves to striated muscles
- sensory information is coming from dorsal column
- motor information is leaving from ventral column
- in the spinal cord, the white matter is on the outside and the gray matter is on the inside. This is because the axons that are travelling towards our CNS are coming from the tips of our limbs. They are coming from a more outer position to a more central position. Therefore, a lot of the cell bodies or ends of the axons would be in the centre of the spinal cord so that they can travel up and synapse towards the top.
Brainstem and Cranial Nerves
◼Midbrain, pons, medulla - together are called brain stem.
◼ Located between the diencephalon and spinal cord. Between thalamus and spinal cord. Thalamus does relay but also do process info.
◼ All of sensory processes passes through thalamus first then goes to the cortex that processes that sensory info . Exception is pain and temperature (goes through ventral collumn). Smell and taste also does not go through thalamus
Lateral surface of brain
- Lateral fissure separates temporal lobe from frontal &
parietal lobes - Central sulcus separates frontal and parietal lobes
- Parieto-occipital sulcus separate parietal and occipital lobes
- Precentral gyrus locates motor cortex
- Postcentral gyrus locates somatic sensory cortex
- Insula cortex is hidden beneath frontal and temporal lobes
Dorsal and ventral surfaces of the brain
- When looking at the brain through the ventral, dorsal view, we can see that the brain is pretty much symmetrical but when looking closely you can see that they are not that symmetrical.
- Bilateral symmetry of cerebral hemispheres
- Corpus callosum bridges the two hemispheres, carrying axons originating from neuron in cerebral cortex of each
hemisphere to contact target neurons in the opposite cortical region.
- organization of movements between both sides of the body.
- need communication between both.
Midsagittal surface of brain
- Calcarine sulcus locates primary visual cortex
- Cingulate gyrus is part of limbic system
- Corpus callosum
- Thalamus is in the middle - relay
- Components of diencephalon:
- Thalamus: relay of sensory and motor signal to relevant primary cortical cortex and also distributer of high order signals from one part of cortical area to another. Does not only play a relay role - also does some processing of somatosensory information.
- Hypothalamus: homeostatic and reproductive functions. Has a role in reproductive functions.
Midsagittal close up of brain
Thalamus
- A cortical relay
◼ The sensory pathways from the eye, ear, and skin all relay in the thalamus before terminating in the cerebral cortex
◼ ~50 nuclear subdivisions maintain distinct inputs & outputs - Receives input from throughout brain and spinal cord
- Sends axons to different cortical areas
- Sends information back to brain stem via internal capsule and basal ganglia
Relay of sensory info versus motor info
- Sensory info from skin, eye, ear reaches the thalamus first and from thalamus reaches the cortex.
- But when it comes to information from motor area, the info goes through internal capsule and reach the spinal cord then muscle.
Internal anatomy of forebrain
◼Amygdala located in front of hippocampus
◼ Basal ganglia (colored image - except for amygdala): caudate, putamen & globus pallidus
◼ Anterior commissure axon tract connecting the two hemispheres
◼ Internal capsule- major pathway linking cerebral cortex to brain & spinal cord
structures you need to know:
- putamen, caudate, internal capsule (bundles of axons that take info from motor area into spinal cord)= input of basal ganglia system
Blood Brain Barrier
◼There is a difference between blood supply to the brain and any other place (shows that the brain is a very importantt organ).
◼BBB protects the brain from toxins & fluctuations in ionic milieu
◼ Interface between walls of capillaries and surrounding tissue are observed throughout the body
◼ In the brain, tight junctions form between capillar endothelial cells that are not seen elsewhere in the body
Often use dyes to figure out the blood supply to different tissues or muscles. This did not work in brain due to the blood brain barrier which did not let molecules from capillary to diffuse to brain.
◼ To enter the brain, molecules must move through endothelial membranes:
-Lipid soluble
- Actively transported e.g. glucose
Meninges
Meninges (Greek for “covering”)
◼ Membranes protecting the brain and spinal cord preventing direct contact with skull or bone
◼ Dura mater: outermost, Latin for “hard mother”
◼ Arachnoid membrane: middle layer with a web-like consistency, from the Greek for “spider”
* Blood vessels and CSF pass between the Dura and Arachnoid membranes. Ruptures to these blood vessles cause subdural hematomas
* Fluid build-up here is dangerous because is puts pressure on the CNS
◼Pia mater: inner layer, adheres closely to the brain and includes many blood vessels, Latin for “gentle mother”
* The Pia is separated from the Arachnoid by the subarachnoid space which contains cerebrospinal fluid (CSF)
Ventricualar system
◼ Ventricles are canals through the brain filled with cerebrospinal fluid (CSF)
◼ Provide useful anatomical landmarks in the brain
◼ CSF is produced by the choroid plexus, special tissue lining the ventricles of the brain
- Produces 500ml CSF/day
- Normal volume in ventricular system is 150ml (3x turnover in one day)
- CSF turnover multiple times daily
◼ CSF flows through the ventricles and exits the CNS into the subarachnoid space by small openings along the dorsal midline of the forebrain, where it is absorbed by subarachnoid villi into the blood
