Lecture_11_BIPN_154_Reivew_II_2025

Animal Models of Anxiety

Elevated Plus Maze

• Purpose: Assess anxiety-related behavior in animals

• Components:

  • Open arms: Represents exposure

  • Closed arms: Represents safety

• Measurement metrics:

  • Total time spent in the open arms

  • Number of entries into open arms

Fear Conditioning Model

Classical Fear Conditioning Paradigm

• Components:

  • Unconditioned Stimulus (US): An aversive stimulus (e.g., electric shock)

  • Conditioned Stimulus (CS): Neutral stimulus paired with US

  • Conditioned Response (CR): Fear response elicited by CS

• Process of Extinction:

  • Gradual dissipation of CR when CS is presented without US

• Relevance: Applicable to understanding anxiety disorders, although not all stimuli-induced anxieties are conditioned

Neural Circuits in Fear Conditioning

Neural Pathways

• Sensory inputs mainly project to the Amygdala; damage hinders fear conditioning

• The Lateral Amygdala (LA):

  • Major site for CS and US convergence

  • Neurons in LA respond to both auditory and nociceptive stimuli

Conditioned Response Pathway

• Central Amygdala (CEA):

  • Projects to brainstem for fear response control

  • Damage disrupts conditioned fear expression

Altered Neuronal Responsivity

• Evidence from studies show increased responsiveness in LA neurons post fear conditioning with CS and US

• Mechanisms of Plasticity in LA:

  • Involvement of NMDA receptors in signaling for long-term changes in response

Amygdala Functions in Anxiety

Projections & Activation

• BLA-CeA Projections:

  • Activation of BLA-CeL shows anxiolytic effects

  • Silencing BLA-CeL leads to increased anxiety (anxiogenic effects)

Animal Models of Stress-Induced Depression

Ideal Model Criteria

• Must exhibit behaviors akin to depression, though all behavioral manifestations are not necessary for validity

Chronic Mild Stress (CMS)

• Behaviors indicative of depression (e.g., reduced sucrose preference) can be reversed with chronic treatment of ADs

• Validity types associated with CMS:

  • Predictive Validity: Consistent behavioral response to chronic treatment

  • Face Validity: Symptoms of depression replicated in model

  • Construct Validity: Decreased responsiveness to rewards as the core symptom

Social Defeat Stress Model

• Induces physiological stress and depressive behaviors reversed by chronic administering ADs

• Results in changes in ACTH and corticosterone levels

Roles of Dopamine in Depressive Behaviors

Dopamine Pathways

• Key regions involved:

  • Mesocortical, Mesolimbic systems

  • Interplay with Raphe Nuclei (serotonin) and Locus Coeruleus (norepinephrine)

Role of VTA Dopaminergic Neurons

• Modulates depression-related behaviors

• Firing rate and behavior correlation observed in tests

Measurement Techniques

Methods for Neuronal Activity

• Fiber Photometry: Measure dynamic Ca2+ changes

• Extracellular Recording: Electrophysiological measurements of neuron activities

• Patch Clamp: Record the properties of synaptic currents and excitability

Behavioral Tests

• Anxiety: Elevated Plus Maze, Open Field Test

• Depression: Sucrose Preference Test, Tail Suspension Test, Social Interaction Test

Summary

• Understanding circuit-specific roles and adaptive behaviors following exposure to stressors aids in grasping anxiety and depression nuances, highlighting the importance of dopamine in these processes.