Lecture 2: Neural Plasticity. Flashcards
What is brain plasticity?
- Brain plasticity is the brain’s ability to reorganize and form new neural connections in response to learning, experience, injury & it enhances cognitive function.
How do life events relate to mood disorders?
- Negative life events near the onset of depressive episodes.
- Associated with the severity of cognitive impairment in depression.
- Patients with depression show:
(1) Increased levels of cortisol in plasma.
(2) Increased CRH in aCSF (cerebrospinal fluid).
What changes occur in the brain with depression?
1) Hippocampal shrinkage (reduction in size).
2) Increased levels of cortisol and CRH in aCSF.
3) Associated with higher levels of stress and increased suicide attempts.
What are the three possible relationships between hippocampal size and PTSD?
1) Development of PTSD causes hippocampal shrinkage.
2) Predisposition scenario: smaller hippocampi in siblings predispose them to PTSD.
3) Stress causes hippocampal shrinkage, regardless of wether PTSD develops (stress independent of PTSD)
What is Early Life Stress (ELS)?
- ELS refers to early traumatic experiences during childhood and adolescence.
- Subtypes of ELS: emotional, physical, sexual abuse, emotional and physical neglect.
- Symptoms:
1) Internalizing symptoms: anxiety, avoidance.
2) Externalizing symptoms: aggresion, hyperactivity.
3) Social impairment.
ELS increases the risk of psychiatric disorders.
How does the 5-HTT gene polymorphism influence stress and depression?
- Polymorphism in the 5-HTT gene (serotonin transporter gene) moderates the influence of stress on depression.
- Individuals with the longer allele of the 5-HTT gene may be less affected by stress, reducing their risk of depression.
How does maternal care influence stress regulation?
(1) Types of maternal care:
- Low LG (licking/grooming) → More stress responses in offspring.
- High LG → Reduced stress responses in offspring.
(2) Maternal care influences the development of the HPA-axis, which regulates stress.
- Low LG offspring → Higher plasma corticosterone levels (stress hormone).
- High LG offspring → Better stress regulation.
What is the role of glucocorticoid receptors (GRs) in stress regulation?
- GRs regulate the body’s stress responses.
-Maternal care influences Gr mRNA expression in the brain.
- Epigenetic changes caused by maternal behavior (e.g., LG) can modify GR expression, impacting stress regulation.
- In humans, GR epigenetic changes are linked to childhood abuse, affecting stress responses later in life.
What is adult neurogenesis?
- The generation of new neurons in the adult brain, particularly in the hippocampus (important for memory and learning).
- Methods to study neurogenesis:
1) H3-thymidine labeling in the dentate gyrus (DG).
2) BrdU labeling in adult human DG.
3) C14 turnover in hippocampal neurons.
4) Markers of progenitor cells to show undetectable neurogenesis in adult DG.
What is Novelty Suppressed Feeding (NSF)?
- A test where anxiety or fear of a new environment suppresses an animal’s feeding behavior.
- Reduced serotonin → Greater anxiety in the NSF test.
- Evidence: Delayed feeding and decreased food intake in novel environments.
What is Chronic Social Defeat Stress (CSDS)?
- Model of stress-induced depression and anxiety in animals.
- Animals are exposed to repeated social stressors (e.g., defeat by an aggressive conspecific).
- Leads to behavioral changes similar to human depression and anxiety.
What is the social interaction test?
- Used to assess social behavior, particularly social avoidance.
- Involves interactions with a novel conspecific (unfamiliar animal of the same species).
- Increased social avoidance: Found in mice with inhibited neurogenesis in the ventral dentate gyrus (vDG).
- Reduced social avoidance: Found in mice with enhanced neurogenesis.
- Social avoidance is indicative of depression-like behavior.
What is synaptic plasticity?
- The ability of synapses to strengthen or weaken over time.
- Long-Term Potentiation (LTP): Strengthening synapses after high-frequency stimulation (linked to learning/memory).
- Long-Term Depression (LTD): Weakening synapses after low-frequency stimulation (involved in memory pruning).
What causes post-partum depression, and how is it treated?
-Caused by delayed recovery of GABAa receptor numbers after pregnancy.
- Prevalent in ~12% of childbearing women.
- Treated with a synthetic neurosteroid during the postpartum period to alleviate mood disorders.
What is transcranial magnetic stimulation (TMS)?
- A method to induce neuroplasticity for treating mental disorders.
- Potentially applies LTP/LTD plasticity to neurological disorder treatment.
What are TetTag mice used for?
- Genetically modified mice using the Tet-On/Tet-Off system.
- Allows for time-specific, reversible control of gene expression via doxycycline.
How is the TetTag model used for negative memory engram studies?
- Negative memory engram cells are neurons activated during memory encoding/storage in the CA1 region of the hippocampus.
- Susceptible mice exhibit higher CA1 negative engram density, correlating with depression-like behavior.
- Inactivation of negative engrams reduces social avoidance.
