BIOL 349 EXAM 1 WVU

Fall 2025

Channelrhodopsin

Light sensitive cation channel; light → Depolarization

Halorhodopsin

Light sensitive Cl- channel; Light → Hyperpolarization

(Bacteriorhodopsin also hyperpolarizes)

Neuropil

Region between cell bodies where most synaptic connectivity occurs

Afferent & Efferent Fibers

Afferent: Periphery → Spinal Cord; Efferent: Spinal Cord → Periphery

Extracellular & Intracellular Recording

Extracellular: temporal patterns; Intracellular: detection of smaller graded changes

Orthologous Genes

Genes present in other animals that are similar to that of human genes

Encephalization Quotient

Brain vs body size

Divergence/ Divergent Evolution

The process through which two or more related species become more dissimilar over time: Adaptations upon a conserved framework. EX. Cerbral cortex evolution

Convergence/ Convergent evolution

The process through which unrelated species develop similar traits or features as a result of adapting to similar environments or ecological niches. EX. Drosophilia and Vertbrate spinal cord developed convergently

Microcephalin Gene Mutation

Smaller head size, decreases stem cell and thus neuron cell production

NOVA1 gene

mRNA splicing in developing human CNS

Human Gene Duplication (ARHGAP11B) (when expressed in other mammals)

Leads to an increase in number of cortical neurons

Fly precursor differentiation

Neural precursor cells differentiate individually

Development before neurogenesis

1) Induction of NS tissue from ectoderm (neuroectoderm & neural stem cells) 2) Movement of neuroectoderm into body (Morphogenesis) 3) Patterning of neural ectoderm (Axes)

Fertilization → Blastula

Cleavage divisions

Gastrulation → Neurulation

Morphogenesis

Chordin & Noggin

Form dorsal-ventral gradient & without them, NS would not develop

BMP4

Ligan secreted by cells that will comprise the ventral embryo

Chordin/Noggin & BMP4 interaction; Organizer

C/N block BMP4 binding. EX. Extra noggin produced during dev → BMP4 blocked over larger area → greater expression of neural ectoderm genes → additional brain and head structures & less epidermis

Gastrulation follows Organizer

organizer moves into embryo and stretches beneath neural ectoderm: Establishing anterior-posterior axis

Neurulation

Neural Plate → Neural tube → moves into embryo: Hinge points determines where neural plate bends to form neural tube (regulated by BMP4 concentration gradients)

Neurulation followed by

Patterning of neural tube (BMP inibitors at head & brain and trunk & spinal cord

Wnt

Promotes growth and devlopment; Wnt inhibtors act on head and brain

Hox genes (transcription factors) (extremely conserved)

Combinatorial expression establishes identity of neural tube; Not expressed in forebrain, midbrain, and cerebellum

Midbrain-Hindbrain boundary (wnt, FGF8)

Pattern midbrain and cerebellum

Ectoderm

Epidermis (Wnt +, BMP +), Trunk (Wnt +, BMP -), Head (Wnt -, BMP -)

Amount of PAX6 (M1 & Anterior S1)+ EMx2 (V1 & posterior S1) correlate

Establishment of cortical areas

Sonic Hedgehog (Shh) gene patterning

Dorsal-Ventral patterning; patterns neural tube midline/ head and face midline; Gradient from ventral-dorsal & medial-lateral activates different combos of transcription factor expression to regulate gene expression

Drosophilia Neurogenesis

After gastrulation, NS forms from the neurogenic region; some cells become neuroblasts while some cells move into the body to create neurons and other cells form epidermis

Preneural clusters

cells express genes that can induce direct formation of neuroblasts; Only a single cell in the cluster will become a neuron

Prenueral clusters express

Notch (receptor) and Delta (ligand) (cell surface proteins); Delta expression regulated by Achaete-scute proteins (ASCs)(transcription factor)

Delta and Notch mechanism

1)Delta binds notch 2) ASC activity blocked 3) delta expression decreased; By random fluctuation, one cell in proneural cluster will produce more delta → notch binding → less ASC → less delta; cells with totally suppressed ASC and delta assume epidermal fate

Cells with most Delta & ASC

They activate bHLH proteins → Neuroblast

Type 1 Neuroblast

Asymmetric division; found in VNC and most of brain

Type 2 neuroblast

Asymmetric division; produces Intermediate progenitors (INPS) which increase in number via Symmetric division

Neuroblast and Neuronal production regulation

Regulated through orientation of mitotic spindle; Straight up = symmetric divsion

Microcephaly on symmetry

No regulation of symmetry: 50% symmetric 50% asymmetric

Timing of vertebrate stem cell division

Early is comprised of symmetric division to build up precursor pool

Asymmetric divsion in mammals produce Intermediate progenitors

IP divides one or more times (more divisions in animals with larger cerebral cortex)

Temporal specification in drosophila (Birthdate-dependent)

Sequential TF expression during each neuroblast division

Mushroom body specification

Gradual decrease in translation of Chinmo RNA due to microRNA encoded by let-7-c gene (regulated by ecdysone circulating hormone); microRNA decrease until no protein is produced

Excitatory/Inhibitory interneuron production

Excitatory produced in subventricular zone; inhibitory produced in ganglion eminences

Mammalian Temporal Specification

Single progenitor sequentially produces different neuron types → new neurons migrate past earlier produced neurons; Production of different neuron types by different progenitors also occurs

C. elegans are model organisms for apoptosis due to ?

All organisms have the same exact amount of cells

Drosophila have most identified neuroblasts where?

Thorax, due to their legs being in that region; motor neurons

Hox gene expression in flies

gives identity to neuroblasts along the anterior-posterior axis; each segment starts with 30 bilateral and 1 median neuroblast; most in abdomen die off, with some dying off only after embryonic neurogenesis

Gene interaction & Neuroblasts (Apoptosis)

Interaction of axis identity genes is determinant of neuroblast fate; Neuroblast 6-4 present in all segments where msh is expressed; Hox gene expression determines fate of neuroblast progeny; Abd-A causes 6-4 to divide symmetrically to produce two glia; Posterior Hox genes (Abd-A & B) block expression of cycE in abdominal segments → terminal symmetric division → two glia produced; cycE expression in thoracic segments produces asymmetric divsion into one glia and one neuronal precursos

Quiescence (Stop dividing) in Neuroblasts

After hatching; except mushroom body neuroblasts

Post-Embryonic neurogenesis

restarts at different times for each neuroblast types followed by apoptosis or terminal cell division; All neuroblasts die by adulthood

Abd-A

a late pulse of expression regulates abdominal neuroblast apoptosis in both embryonic and post embryonic stages; different interaction mechanism depending on embryonic or post embryonic (cas TF)

Neuronal Apoptosis

Anterior MP1s & dMP2s (grim rpr) → apoptosis; Posterior MP1s & dMP2s (Abd-B blocks grm rpr) → survival

Hox gene dependent with early embryonic MP neurons

Post embryonic apoptosis → asymmetric localization of numb → asymmetric signaling and expression by notch (receptor and promotes differentiation)

Vertebrate apoptosis

Occurs throughout development (to remove ‘mistakes’)

Neurotrophins

diffusible factors that regulate neuron apoptosis in vertebrates & drosophila and regulate neuron numbers; NO neurotrophins = no growth

EX. of trophic factor removal

Nucleus of bulbocavernosis in mammalian spinal cord

in male rats, MNs here innervate muscles necessary for erection and urination in rats, in females the muscles are greatly reduced and MNs absent but in early development the muscles and MNs present in both sexes

Testosterone→ muscle development → MN survival

Other ex. turtles have no thoracic muscles and near absent spinal cord thoracic MNs while dinosaur ancestors had leg muscles and greatly expanded MN pools

Neurites

processes which form axons and dendrites

Pathfinding process

1) growth cones follow chemical cues to their target 2) Synapse formation 3) synapse refinement and pruning

Chemoattractants(+) and chemorepellants(-)

Long range cues(+:netrins, -:semaphorins), Short range( +: cadherin, -:ephrins)

Chemattractant process

Cue binds membrane receptor → Ca2+ influx → actin & microtubule polymerization

Guidepost cells and Pioneer neurons

physical pathways for growth cones; In cortex, radial glia physically guide neurons to the proper layers

Transient subplate neurons (different in mouse vs primate)

Electrically active; guides input from lateral genticulate nucleus (LGN) to cortex & assists in synapse formation on newborn cortex neurons; Input axons may be held at subplate until target neuron is mature

Commissural Neuron growth cones (Midline crossing)

Attraction to midline → enter midline → leave midline on opposite side

EX. fly loss of function mutation: slit(growth cones can enter but cannot be repelled from midline)

robo(continuous attraction to midline)(second robo gene still active driving difference between slit & robo LOF phenotypes)

comm (cannot enter midline)

Protein regulators of midline crossing

Netrin: Attractive cue, ligand; DCC: Netrin receptor

Slit: repulsive cue, ligand; Robo: Slit receptor

Growth cone chemical necessities