11.1 Neuroplasticity and Synaptic Changes

Neuroplasticity is the brain's ability to change and adapt. This section explores how synapses strengthen or weaken over time, and the molecular mechanisms behind these changes. It also covers structural changes in neurons and the formation of new brain cells.

Experience-dependent plasticity shows how our brains change based on what we learn and do. This part also looks at adaptive plasticity, which helps us recover from injuries, and maladaptive plasticity, which can lead to problems like chronic pain or addiction.

Synaptic Plasticity Mechanisms

Long-Term Synaptic Changes

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• Synaptic plasticity refers to the ability of synapses to strengthen or weaken over time in response to increases or decreases in their activity
• Long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity resulting in a long-lasting increase in signal transmission between neurons
• Long-term depression (LTD) is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus (low-frequency stimulation)
• Hebbian learning suggests that an increase in synaptic efficacy arises from the presynaptic cell's repeated and persistent stimulation of the postsynaptic cell meaning neurons that fire together, wire together

Molecular Mechanisms of Synaptic Plasticity

• LTP is induced by high-frequency stimulation and involves the activation of NMDA receptors, calcium influx, and subsequent activation of kinases (CaMKII, PKC) leading to increased AMPA receptor insertion and enhanced synaptic strength
• LTD is induced by low-frequency stimulation and involves the activation of phosphatases (calcineurin, PP1) resulting in AMPA receptor endocytosis and decreased synaptic strength
• Hebbian plasticity involves the coincident activation of pre- and postsynaptic neurons causing NMDA receptor activation, calcium influx, and CaMKII activation leading to increased AMPA receptor trafficking and enhanced synaptic efficacy (spike-timing-dependent plasticity)
• Synaptic plasticity is also regulated by neuromodulators (dopamine, norepinephrine) and neurotrophic factors (BDNF) that can modulate the induction and maintenance of LTP and LTD

Structural Changes in Neuroplasticity

Dendritic and Axonal Remodeling

• Dendritic spine remodeling involves changes in the shape, size, and number of dendritic spines in response to synaptic activity and is associated with synaptic plasticity and memory formation
• Axonal sprouting refers to the growth of new axonal branches from existing axons allowing neurons to form new synaptic connections and reorganize neural circuits in response to experience or injury
• Synaptogenesis is the formation of new synapses between neurons and is important for learning, memory, and recovery from brain injury
• Pruning is the selective elimination of synapses and neurons during development and throughout life to refine neural circuits and optimize brain function

Neurogenesis and Gliogenesis

• Neurogenesis is the birth of new neurons from neural stem cells and occurs primarily in the hippocampus and subventricular zone of the adult brain contributing to learning, memory, and mood regulation
• Gliogenesis is the formation of new glial cells (astrocytes, oligodendrocytes) from glial progenitor cells and is important for supporting neuronal function, myelination, and brain repair after injury
• Experience and environmental factors (enriched environment, exercise, stress) can modulate the rate of neurogenesis and gliogenesis in the adult brain impacting brain plasticity and behavior
• Neurotrophic factors (BDNF, NGF) and transcription factors (CREB, NeuroD) regulate the proliferation, differentiation, and survival of new neurons and glial cells in the adult brain

Types of Neuroplasticity

Experience-Dependent Plasticity

• Neuroplasticity refers to the brain's ability to change and adapt in response to experience, learning, and environmental stimuli throughout life
• Experience-dependent plasticity is the modification of neural circuits and synapses in response to specific experiences or sensory inputs leading to the acquisition of new skills, knowledge, and behaviors
• Examples of experience-dependent plasticity include:
  • Learning a new language or musical instrument
  • Acquiring motor skills through practice (juggling, dancing)
  • Developing enhanced sensory perception in specific domains (visual acuity in artists, auditory discrimination in musicians)
• Critical periods are windows of heightened plasticity during development when the brain is particularly sensitive to specific experiences and environmental inputs (language acquisition, visual development)

Adaptive and Maladaptive Plasticity

• Adaptive plasticity refers to beneficial changes in neural circuits and behavior that promote learning, memory, and functional recovery after brain injury or disease
• Examples of adaptive plasticity include:
  • Cognitive reserve, which is the brain's ability to maintain function despite age-related changes or pathology due to a lifetime of learning and experiences
  • Cross-modal plasticity, where the loss of one sensory modality (vision) leads to the enhanced processing of other senses (hearing, touch) in the deprived cortical areas
• Maladaptive plasticity refers to detrimental changes in neural circuits and behavior that contribute to the development or maintenance of neurological and psychiatric disorders
• Examples of maladaptive plasticity include:
  • Chronic pain, where persistent nociceptive input leads to the sensitization of pain pathways and the expansion of pain-responsive cortical areas
  • Addiction, where repeated drug use induces long-lasting changes in reward circuits and decision-making processes leading to compulsive drug-seeking behavior