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Neuroplasticity and Neurogenesis in Health and Disease

Course Information

  • Instructor: Prof. Dr. Clarissa Cavarsan (she, her, hers)

  • Program: Neuroscience and Behavior Program

  • Course: NS&B 360 – 01 Neuroplasticity and Neurogenesis in Health and Disease

  • Semester: Spring 2026

Running and Neuroplasticity

Source:

  • All About Running: Synaptic Plasticity, Growth Factors and Adult Hippocampal Neurogenesis

  • Authors: Carmen Vivar, Michelle C. Potter, Henriette van Praag

  • Citation: Curr Topics Behav Neurosci (2013) 15: 189–210

Key Concepts

Exercise and Cognition

  • Neurogenesis: The formation of new neurons in the brain, particularly in the hippocampus.

  • Cognition Studies in Animal Models:

    • Adult rodents (both voluntary and forced exercise) show enhanced spatial memory in the following tests:

      • Morris water maze

      • Y-maze

      • T-maze

      • Radial arm maze

    • References: Fordyce and Farrar (1991), van Praag (2008).

Exercise and Neurogenesis

  • Intrinsic and Extrinsic Factors: Regulation of new neuron production is influenced by various factors.

  • Hippocampal-Spatial Learning: Increased neurogenesis correlates with improved performance in the Morris water maze.

  • Mid-term Memory: Rats that engaged in treadmill running showed better memory performance and swimming speed related to the platform's quadrant in the maze test.

Effects of Exercise on Synaptic Plasticity

Types of Exercise

  • Aerobic vs. Resistance Exercise: Both types lead to increased cerebral blood flow, neural progenitor cells proliferation, neurogenesis, and enhanced memory.

Neurotrophic Factors

  • Exercise-Induced Factors: Exercise activates trophic and neuroprotective release factors.

    • BDNF: Brain-derived neurotrophic factor, mRNA and synaptic protein levels are increased in the dentate gyrus (DG) and amygdala due to exercise.

    • Importance: BDNF is crucial for synaptic plasticity, learning, and neurogenesis.

    • Observations: Protein levels rise after 3 weeks of exercise and fall post-exercise, correlating with radial water maze performance.

Synaptic Plasticity and Long-Term Potentiation/Depression (LTP/LTD)

  • Running's Influence:

    • Modifications in synaptic function occur due to exercise.

    • Enhanced LTP was observed in various studies including those by Farmer et al. (2004) and O’Callaghan et al. (2007).

Neurotransmitter Systems Affected by Exercise

  • Exercise influences the following neurotransmitter systems:

    • Glutamatergic (Farmer et al. 2004; Kitamura et al. 2003)

    • GABAergic (Molteni et al. 2002)

    • Endocannabinoid (Hill et al. 2010)

    • Opioidergic (Sforzo et al. 1986)

    • Monoaminergic (Chaouloff 1989)

Aging and Exercise

  • Effects of Aging: Age brings functional changes to the hippocampus, crucial for learning tasks:

    • Studies indicate decreased learning ability with age (Gage et al., 1984; Smith et al., 2000).

    • Animals engaged in voluntary and forced exercise demonstrated better performance compared to sedentary controls in various behavioral tasks.

Conditioning and Fear Learning

Ivan Pavlov's Classical Conditioning

  • Process:

    • Before Conditioning: Unconditioned stimulus (US) causes unconditioned response (UR) with a neutral stimulus (NS) producing no response.

    • During Conditioning: The US and NS are paired.

    • After Conditioning: NS becomes a conditioned stimulus (CS), eliciting a conditioned response (CR).

Fear Conditioning

  • Types: Cued (Tone) FC and Contextual FC involve associations made with stimuli and experiences.

Neural Circuits in Fear Conditioning

  • Involvement of Brain Areas:

    • The lateral nucleus of the amygdala (LA) receives inputs from thalamic and cortical auditory/somatosensory regions.

    • Other areas of interest: Central grey (CG), lateral hypothalamus (LH), and paraventricular hypothalamus (PVN).

Neurodegenerative Diseases and Exercise

Effects on Aging and Neurogenic Diseases

  • Reduced Neurogenesis: Common in aging and observed in certain neurodegenerative mouse models.

  • Alzheimer's Disease (AD) Models: Exercise reduces pathology and enhances cognition, boosting adult neurogenesis.

  • Exercise and Huntington's Disease (HD) Models: Negative effects observed, including exacerbating locomotor deficits.

Neurophysiological and Neurochemical Effects of Exercise

Key Findings

  • HPA Axis (Hypothalamic-Pituitary-Adrenal Axis): Exercise promotes positive changes, including cortisol reduction, increased antioxidant activity, and cerebral blood flow.

  • Neurotransmitter Levels: Exercise upregulates neurotransmitter activity, including GABA, norepinefrine, dopamine, and serotonin, positively impacting the opioid system.

  • Neurotrophic Factors: Increases in BDNF, IGF-1, VEGF, NT3, and others promoting neurogenesis and synaptogenesis.

Negative Impacts of Stress

  • Stress-Induced Changes: Can disturb cell signaling pathways, affecting neurogenesis and promoting cognitive deficits.

Conclusion

  • Comprehensive Benefits of Exercise: The effects include enhanced neurogenesis, modifications in synaptic plasticity, increased spine density, neurotrophins, and angiogenesis. These play vital roles in improving learning and memory, reducing neurodegenerative disease risk, and delaying cognitive decline with age.

  • Research Needs: More investigations are required to dissect the cellular mechanisms behind aerobic activity effects on the brain, emphasizing exercise as a viable intervention for maintaining cognitive function throughout life.