7*** Genetic Modifications in Neuroscience

Vocabulary flashcards covering key methods and concepts in genetic modification, gene targeting, transgenic models, viral vectors, CRISPR-Cas9, optogenetics, and chemogenetics from the lecture notes.

Genetically Modified Model

An organism whose genome has been intentionally altered through the use of genetic engineering techniques.

Reverse Genetics

An experimental research strategy where scientists alter or remove a known gene to investigate its biological function ($\text{gene} \rightarrow \text{function}$).

"P" Rats

A rat model created through selective breeding specifically chosen and bred for a high preference to drink alcohol.

Gene Targeting

A precise genetic engineering technique used to alter, knock out, or replace a specific gene at its endogenous location in an organism's DNA.

Knockout (KO) Model

An animal model created by replacing a functional gene with a nonfunctional sequence, completely disabling or ablating that gene to observe what biological functions are affected.

Homozygous Knockout ($-/-$)

A genetic notation designating an organism in which both alleles of a specific gene have been completely deleted or inactivated (e.g., $\text{DAT}^{-/-}$).

Heterozygous Knockout ($+/-$)

A genetic notation indicating that an organism carries one functional copy and one inactivated copy of a targeted gene.

Knock-in (KI) Model

A model produced by gene targeting where a specific DNA construct is inserted at a particular locus to introduce a new element, such as a reporter gene, a human disease allele, or a defined mutation.

Transgenic Organism

An organism that contains foreign DNA—either from another species or an engineered variant—intentionally integrated into its genome (e.g., mice expressing human APP to model Alzheimer's disease).

Green Fluorescent Protein (GFP)

A fluorescent protein originally derived from the jellyfish Aequorea victoria used as a visual reporter or biological "flashlight" to track gene expression and cellular structures in living tissues.

Viral Vector

A modified virus engineered to deliver genetic cargo into host cells, commonly used to introduce genes for opsins, DREADDs, or fluorescent markers into targeted brain regions.

CRISPR-Cas9

A precise gene-editing system derived from bacterial viral defense mechanisms, composed of a guide RNA that locates a complementary DNA sequence and a Cas9 nuclease that cuts the double-stranded DNA.

Southern Blot

A molecular biology assay that hybridizes labeled probes to specific fragments of digested DNA, typically utilized for initial validation of gene-targeted recombinant alleles.

Polymerase Chain Reaction (PCR)

A molecular biology technique used to rapidly amplify defined segments of DNA, serving as the standard method for ongoing animal genotyping.

DREADDs

Designer Receptors Exclusively Activated by Designer Drugs; engineered G-protein coupled receptors introduced into neurons that remain inert until activated or inhibited by synthetic ligands (such as CNO or DCZ).

Optogenetics

A technique using light to modulate the electrical activity of neurons that have been genetically modified to express light-sensitive proteins (opsins) with millisecond temporal precision.

Channelrhodopsin-2 (ChR2)

A light-gated cation channel originating from green algae that opens in response to blue light ($460\,\text{nm}$) to permit $\text{Na}^+$ influx, depolarizing and exciting the host neuron.

Halorhodopsin

A light-sensitive protein that activates in response to yellow light ($580\,\text{nm}$) to drive $\text{Cl}^-$ influx into the cell, hyperpolarizing and inhibiting neuronal firing.

Optrode

An integrated laboratory tool combining a fiber-optic cable for light delivery with an extracellular microelectrode for simultaneous recording of neural electrical activity.

Dopamine Transporter (DAT)

A plasma membrane transport protein responsible for the reuptake of dopamine from the extracellular space back into presynaptic terminals.

Serotonin Transporter (SERT)

A monoamine transporter that removes serotonin ($\text{5-HT}$) from the synaptic cleft into presynaptic neurons, commonly evaluated in knockout models studying mood and reward systems.