Diencephalon

• positioned between the brainstem and telencephalon
• two symmetric halves separated by the third ventricle
• rostrally, the diencephalon is seperated from the telencephalon by the collection of the interventricular foramen, the lamina terminalis and the optic chiasm
• at the midle, the junction between the diencephalon and midbrain lies along a line extending from the caudal edge of the mammillary body to the posterior commisure
• laterally, the internal capsule separates the diencephalon from the telencephalon

Dorsal Thalamus

• gateway
• covered and subdivided by thin sheets of myelinated axons
• lateral covering is called the external medullary lamina. internal medullary lamina(within thalamus) subdivides the thalamus
• subdivisions: anterior thalamic, medial thalamic, lateral thalamic nuclei
• anterior nuclei is to recieve and send info tied to the limbic system

Dorsal thalamus

Medial Thalamic Nuclei

• major nucleus of the medial thalamic subdivision is the mediodorsal nucleus
• major functions of the mediodorsal nucleus include: mood, personality, emotion, eye movement

Dorsal Thalamus

Lateral Thalamic Nuclei

• divided into two tiers
• dorsal tier: Lateral Dorsal(LD), lateral poserior(LP), and pulvinar (found in lab)
• Ventral Tier: VA, VL, VP, VPM, LGN, MGB: explained on another card

Lateral Thalamic Nuclei

Ventral Tier

• Ventral Anterior(VA): Motor
• Ventral Lateral(VL): Motor
• Ventral Posterolateral (VPL): Somatosensory (from body)
• Ventral Posteromedial (VPM): Somatosensory (from face, CN V)
• Lateral Geniculate Nucleus (LGN): Vision (bump)
• Medial Geniculate Body (MGB): Auditory (bump)

Hypothalamus

• collection of nuclei that regulate homeostatic functions via the autonomic nervous system and endocrine activities
• rough "triangle" formed by the anterior commissure, the mammillary bodies(which are part of the diencephalon) and the optic chiasm 
• collection of functionally distinct nuclei

Epithalamus

• prominent structures of the epithalamus are the pineal gland, habenula and the stria medullaris
• pineal gland: production of melatonin
• habenula: motivation control of behavior, anterior to pineal gland
• stria medullaris thalami: fiber tract located on the dorsomedial aspect of the dorsal thalamus

Ventral Thalamus

• only nuclei of the ventral thalamus we will discuss is the subthalamic nucleus
• subthalamic nucleus is located posterior to hypothalamus
• involved in movement and associated with the basal ganglia
• most readily identified in coronal slabs

Thalamogeniculate Stroke

• blood supply to the diencephalon
• loss of sensory relay(hemianesthesia) through the ventral posterior (VPL(dorsal column)/VPM(trigeminal) nuclei

Internal capsule

• large fiber tract that connects the dorsal thalamus to the cerebral cortex(also connects cortex to the brainstem and spinal cord)
• part of the telencephalon
• useful landmark when you are look at the wet specimens in the laboratory

Telencephalon

• two large hemispheres of cerebral cortex(gray matter)
• deep fissure called the longitudinal fissure separates these hemispheres
• groove and valley appearance of the cerebral cortex occurs as the cortex folds on itself to allow for more surface area
• below the cerebral cortex is an expansive region of subcortical white matter that carries neural connections to and from cortex
• buried in the telencephalon are structures with various functions: basal ganglia, hippocampus and amygdala

Cerebral Cortex

• cerebral cortex is the major brain area associated with perception, consciousness and higher thought
• cerebral cortex coves nearly the entire surface of the cerebral hemispheres and is a layered structure
• most cortex is 6 layered(neocortex)
• a couple restricted areas of cerebral cortex contain 3 layers: archicortex(hippocampus) and paleocortex (olfaction)

Cerebral Cortex

Frontal

• contains precentral gyrus/primary motor cortex/Brodmann Area 4
• genreal functions: motor, speech, executuive functions(judgment, planning and problem solving)

Cerebral Cortex

Parietal

• contains postcentral gyrus/primary somatosensory cortex
• general functions: somatosensation, high-level visual processing, sensory integration, attention

Cerebral Cortex

Occipital 

• contains visual cortices

Cerebral Cortex

Temporal

• contains primary auditory cortex
• general functions: audition, high-level visual processing, olfactory processing, memory

Subcortical White Matter

• projection fibers internal capsule: genu, anterior and posterior limb
• commissural fibers: corpus callosum(rostrum, genu, body, splenium), anterior and posterior commissure
• associated fibers

Internal capsule

• contains fibers traveling to and from the cerebral cortex (anterior limb, genu, posterior limb)
• ascending fibers are from thalamic nuclei
• descending fibers are from the cerebral cortex and targeting subcortical nuclei and the spinal cord
• corticobulbar is at the genu(cortex to cranial nerves)
• frontopontine and thalamic are more anterior to the genu

Internal Capsule

Genu

• this is the bend in the internal capsule
• contains fibers from recentral gyrus that project down to motor nuclei of the cranial nerves
• corticobulbar fibers in genu(cortex to brainstem)

Internal Capsule

Anterior Limb

• contains fibers that interconnect the dorsomedial and anteriorthalamic nuclei with the frontal and cingulate gyrus

Internal Capsule

Posterior Limb

• larger than anterior limb
• anterior portion primarily contains motor fibers (corticospinal)
• posterior portion primarily contains somatosensory, auditory and visual fibers(sensory, temporopontine, visual and auditory)

Commissural Fibers

• commissural fibers connect left and right hemispheres
• corpus callosum: huge commisure that forms the roof of most of the lateral ventricles(4 parts)
• anterior commissure: located rostral to the collums of the fornix, interconnects various regions of the frontal and temporal lobes
• posterior commissure: located rostral to the superior colliculus. interconnects caudal parts of the diencephalon (pupillary light reflex)

Association Fibers

• fibers that connect areas of cerebral cortex within the same hemisphere
• you do not need to know names of individual pathways

Basal Ganglia

• caudate: head and tail
• putamen
• globus pallidus: internal and external
• combined, the caudate nucleus and the putamen and the striatum
• combined, the putamen and the globus pallidus is the lentiform nucleus
• basal ganglia has an extensive role in movement
• convoluted C shaped structure

Hippocampus

• seahorse
• located internal to the parahippocampal gyrus
• forms a medial wall of the inferior horn of the lateral ventricle
• memory 

Fornix

• prominent white matter structure
• connects the hippocampus to the hypothalamus and septal nuclei
• collumns of fornix dive down towards hypothalamus

Amygdala

• located medially within the temporal lobe
• internal to the uncus
• anterior to the hippocampus
• process emotions 
• classically fear

Telencephalon

Blood Supply

• Anterior cerebral artery/brances: major targets frontal and parietal lobes
• middle cerebral artery/branches: all lobes and the basal ganglia via the lenticulostriate arteries
• Posterior cerebral artery/branches: occipital, temporal and parietal lobes
• basal ganglia is middle and anterior CA and thalamus is primarly posterior CA (genicular arteries)

Ohms Law

• V=IxR
• ionic currents that flow across a membrane depend on the resistance of the membrane and the voltage across it

Ion Equilibrium

• use nernst equation
• Ek= -58 to -80
• ENa = +45 to +60
• high concentration of Na outside of cell and high concentration 
• Use goldman equation for when a membrane is permeable to multiple ions

Subarachnoid Cisterns

• enlargements of the subarachnoid space named according to what they border
• pontine, interpeduncular, chiasmic, superior, cerobellomedulary, and lumbar

Lipofuscin

• by product from high metabolic activity of neurons
• yellow-pigment granule can be seen in cell bodies
• if acculated too much, lipofuscin can damage neurons, causing degeneration

Undershoot of Action potential

• membrane hyperpolarizes becauses Na channels were inactivated so only K working
• causes K to go down to its equilibrium of around -80 instead of the resting potential of -65

Tetrodotoxin

• blocks Na Current
• used to analyze pottasium current of action potentials
• most blocked, pufferfish poison
• shows rapid inactivation
• activation of K current is delayed, which allows a little bit of action potential 

Tetraethyl-ammonium

• blocks pottasium channels
• used to analyze the Na current in an action potential
• shows no inactivation

Potassium and Sodium conductance

• both increase as the membrane charge becomes more positive (depolarization)
• Sodium goes up and down and pottassium goes up then plateaus 

Conduction Velocity

• two main ways to increase how fast an action potential propagates down an axon
• increase the diameter of the axon-large diameter axons have a lower resistance to current flow within the cytoplasm of the axon and so conduct faster than smaller diameter ones
• insulate the axon to prevent current from leaking out-myelinated verss unmelinated nerve fibers (saltatory)

Patch clamp Method

• cell-attached recording
• mild suction (tight contact btw pippette and membrane
• whole cell recording(strong pulse of suction, cytoplasm is continuous with pipette interior)
• inside out recording(expose to air, cytoplasmic domain accessible)
• outside out recording (retract pipette, end of membrane anneal, extracellular domain accessible)

common voltage gated channels

• Na channel
• Ca channel
• K channel
• Cl- channel 

Voltage Gated Sodium Channels

• start out closed(but not inactivated)
• then becomes open
• after some time the gate stays opeb but becomes inactivated 
• then eventually goes back to closed but not inactivated 
• potassium is either open or closed (no inactivating gate)

2-P channel

• pottasium channel that does not have a voltage sensory
• leaky channel responsible for setting membrane resting potential

Ligand gated channel examples

• neurotransmitter receptors: Na/K exchanger using glatamate to activate
• Ca2+ activated K channel
• Cyclic nucleotide gated channel(Na/k exchanger)

2 types of Ligand Gated Channels

• ionotrophic: receptor and the ion channel are a single entity 
• metabotrophic: the receptor and ion channel are two distinct entities (dependent on metabolism)
• movement of ions not specific but depends on equilibrium potential
• at 0 mv the equilibrium potential of Na and K directly oppose each other (equal and opposite), no synaptic potential

ACh Receptor

• ligand-gated nicotinic receptor(ionotrophic
• has a extracellular, transmembrane and cytoplasmic domain
• 2 alpha subunit, delta, beta and gama subunit
• both alpha subunits have to bind ACh for channel to open (must have high ACh concentration 

Glutamate Receptor

• ionotrophic
• AMPA receptor(common in brain for neuron transmission)
• Amino terminal domain(ATD), Ligand binding domain(LBD), transmembrane, carboxyl-terminal domain(CTD)
• when ligand binds clam closes and pulls open pore

NMDA Receptors

• ionotrophic
• Glycine and glutamate binding sites
• glutamate requires bind of glycine too
• GluN2A, GluN1, GluN2A
• most allow sodium and pottasium to flow through like others
• Mg blocks the NMDA receptor at rest(hyperpolarized)
• no Mg blocking it when depolarized
• Ca and Na flow in and K flows out 
• ligand because even if depolarized, it will not open without glutamate

Electrical Synapse

• gap junction channels
• each cell has a connexon(hemichannel) that combine to form one channel
• each hemichannel has six identical subunits(connexin)
• fast large pores, non selective
• generally bidirectional
• synchronization
• development
• glial cells (common in these in adults)
• clinical note: genetic deafness (from these in inner ear)

Presynaptic Terminal

• presynaptic cell makes the chemicals(transmitters)
• presynaptic terminals store, release, and recycle transmitters
• transmitter vesicles contain highly concentrated transmitters
• active zones: presynaptic sites of transmitter release
• voltage-gated Ca2+ channels

Electrical Vs Chemical Transmission

• fast vs of a delay(0.5ms)
• no signal amplification vs amplification
• bidirectional vs unidirectional
• not plastic vs plastic(can be regulated, flexible)

Synaptic Vesicle Membrane Proteins

• synaptotagmin: Ca2+ binding
• synaptobrevin: SNARE component
• Transmitter transporters: transports transmitter molecules from outside into vessicles
• proton pump: energy for transporters(build up of hydrogen inside vessicle used for energy)

SNARE Complex

• synaptobrevin(synaptic vessicle
• SNAP-25 and syntaxin on plasma membrane 
• brings vessicle towards plasma membrane so that the vessicle can fuse
• certain neurotoxins, botulinum, can destroy SNARE proteins (paralysis of signal)
• Tetanus toxin destroys synaptobrevin

Transmitter Receptors

• Direct gating(transmitter causes open only)
• indirect gating( open/close)

Transmission Termination

• diffusion(glial cell)
• enzymatic destruction (major pathway for cholinergic transmission, ACh)
• re-uptake

Life Cycle of Glutamate

• Glutamate is either reuptaken by presynaptic terminal or a glial cell using differentExcitatory amino acid tansporters (EAAT)
• Glutamine Synthetase then converts glutamate to glutamine in the Glial cell
• Glutamine transporter out of Glial Cell (SN1) and transported into presynaptic terminal (SAT2)
• Glutamine can also just use diffusion
• Glutaminase (made in cell body and transported) converts glutamine to glutamate inside presynaptic terminal
• VGluT transports glutamate into vessicle

GABA life Cycle

• most abundant inhibitory transmittor in brain
• GABA can be ruptaken by GAT(GABA tansporter) in presynap terminal or glial cells
• in glial cells GABA transaminase converts GABA to glutamate
• Glutamate converted to glutamine and diffuses out and then into presyn term
• glutaminase converts gln to glu
• Glutamic acid decarboxlase(GAD) creates GABA from Glu
• VIAAT loads GABA into vessicle

Acetylcholinesterase

AChE

• breaks down ACh to acetate and choline
• choline is reuptaken by Choline transporter
• choline acetyltansferase(ChAT) then drives reaction to make acetyl choline again
• happens at Neuromuscular junction

Classic Neurotransmitters

• acetylcholine
• 3 amino acids: glutamate, GABA, and glycine
• 5 biogenic amines: dopamine, NE, Epinephrine, serotonin, histamine

Non-classical neurotransmitters

• neuroactive peptides (made in cell body only)
• stored in dense-core vesicles
• released in response to general intracellular Ca increase
• no reuptake
• longer actions

Types of Synaptic Connections

• axodendritic (often excitatory)
• Axosomatic (often inhibitory)
• axoaxonic (often modulatory)
• dendrodendritic
• excitatory vessicles generally round and membrane asymetrical(post syn thicker) and inhibitory are oval and membranes are symetrical in thickness

ACh Receptors

• ionotropic receptors: nicotinic receptors (curare inhibits)
• Metabotropic receptors: muscarinic receptors (atropine inhibits)

Nicotinic Receptors

• pentamer (5 subunits): 2 alpha, beta, gama, delta
• 2 ACh molecules bind each receptor
• more Na enter than K leave the cell (Driving force=RMP-E)
• can also have 2alpha 3 beta or 5 alpha
• number of ACh needed is equal to number of alpha subunits
• not permeable to anions because receptor has three rings of negativly charged Glu and Asp

Glutamate Receptors

(iGluRs)

• Ionotrophic either non-NMDARs or NMDAR
• Non-NMDARs are either AMPAR or Kainate-R
• all named for things that can activate
• Metabotropic receptors: 8 different receptors that fall into three different groups

AMPA Receptor

• tetramer(4 subunits)
• 2 glutamate molecules bind each receptor
• more Na influx then K efflux
• some are Ca permeable

NMDA Receptor

• tetramer(4 subunits)
• 2 glutamate molecules bind each receptor
• cofactor: glycine
• highly Ca permeable
• more Na and Ca influx than K efflux
• normally blocked by Mg during hyperpolarization, depolarization removes it
• synaptic plasticity 
• can cause excitotoxicity from too much glutamate
• PCP blocks

Phencyclidine

GABA Receptors

• ionotropic receptors: GABAaR and GABAcR
• metabotropic receptors: GABAbR
• gabazine inhibits and muscimol and GABA activate GABAaR
• phaclofen inhibits and Baclofen and GABA activate GABAbR

GABAaR

• [similar to nAChR
• ionotropic
• pentamer(5 subunits
• 2 GABA molecules bind eachr eceptor
• many drug binding sites
• Cl influx (most cases in adult brain)

Glycine Receptor

• 3 alpha and 2 beta subunit
• similar to nAChR
• need three glycine molecules to bind
• opening allows influx of Cl, causing hyperpolarization
• only ionotropic receptors, no metabotropic ones

Reticular Formation

• located in the tegmentum of entire brainstem
• many discrete nuclei organized by spec functions, and groups, and columns, and neurotransmitters used
• functions: autonomic centers(resp, cardio, ect), pain system(antereolateral system inputs and modulation), motor system(reticulospinal tracts and gaze centers), 

Reticular Formation Tracts

• central tegmental tr: ascending(taste, visceral) and descending (red nucleus and motor control)
• dorsal longitudinal fasciculus: connects RF and hypothalamus
• medial forebrain bundle: connects RF and septum/basal forebrain

Reticular Formation

Small nuclei projections

• divergent (project to huge number of structures)
• diffuse (project all over in those structures)
• allows effects to be widespread and often non-specific

Dopamine

• locus coeruleus(also makes/uses NE)
• substantia nigra pars compacta
• ventral tegmental area(on either side of midline)
• hypothalamus
• nucleus accumbens (bottom of internal capsule)
• projections into diencephalon and all over cerebrum

Dopamine

Ventral Tegmental Area

• on either side of midline with myelin running through
• mesocortical: projections to frontal lobe, especially prefrontal cortex(meso-refers to its origin in midbrain)
• mesolimbic: projections to numerous limbic areas, especially nucleus accumbens(ventral striatum) and septal nuclei
• clinical issues: dementia(frontal cortex, psychosis (schizophrenia), drug addiction (mesolimbic)

Norepinephrine

• locus ceruleus(A6) (in the pons)
• others are A1-A7
• find it dorsal to the CN V
• projections go to forebrain(cortex), cerebellum, diencephalon, brainstem, and spinal cord
• functions: sleep, stress response, pain modulation (spinal cord proj, descending), cognition, mood
• Clinical issues: Depression(tricyclic antideprs, MOA inhibitors, SNR1(for ADHD too), PTSD, irritable bowel syndrome, some depression

Serotonin(5HT)

• all 5HT made in raphe nuclei (on midline throughout brainstem)
• projections: forebrain (cortex), cerebellum, thalamus, brainstem, spinal cord
• functions: sleep, pain modulation, mood, anxiety
• depression and axiety treated with Selective serotonin reuptake inh (prolong action of serotonin, prozae, paxil, and zoloft)

Acetylcholine ACh

Basal forebrain

• basal forebrain: septal nu, diagnonal band nu, and nu basalis
• projections: cortex and amygdala
• functions: learning and memory, limbic system function
• clinical issues: dementia, alzheimers disease

Acetylcholine (ACh)

Brainstem group

• Peduncular Pontine Tegmental and Lateral dorsal Tegmental
• projections: thalamus and basal forebrain cholinergic parts
• functions: sleep, arousal, consciousness
• clinical issues: coma and sleep disorders

Ascending Reticular Activating System

(ARAS)

• brainstem components: locus ceruleus(NE), pedunculopontine tegmental nu(PPT, cholinergic), laterodorsal tegmental nu(LDT, cholinergic)
• outputs to: thalamus(intralamin nuclei(pain, and other nuclei(LGN, VPM); basal forebrain cholinergic nuclei
• bilateral damage(rigidity, spasticity, coma)
• function: increase level of arousal: threatening situations, weken from sleep, external and internal stimuli