6.4 Adult neurogenesis and synaptic plasticity
4 min read•august 14, 2024
Adult brains can grow new neurons in specific areas, challenging old beliefs. This process, called , happens in the and near the brain's fluid-filled spaces. It's affected by things like stress, exercise, and our surroundings.
Synaptic plasticity is how brain connections change strength based on experience. It's key for learning and memory, allowing our brains to adapt. This happens all over the brain, not just in memory areas, helping us learn facts, skills, and emotions.
Adult neurogenesis and its regions
Process and brain regions
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- Adult neurogenesis is the process by which new neurons are generated in the adult brain, challenging the long-held belief that the adult brain is incapable of producing new neurons
- Neurogenesis primarily occurs in two regions of the adult brain: the subgranular zone (SGZ) of the dentate gyrus in the hippocampus and the (SVZ) of the lateral ventricles
- Various factors, such as age, stress, exercise (running), and (complex housing), can influence the rate of adult neurogenesis in the brain
Stages of adult neurogenesis
- In the SGZ, neural stem cells give rise to intermediate progenitor cells, which then differentiate into immature neurons and eventually mature into functional granule cells that integrate into the existing hippocampal circuitry
- In the SVZ, neural stem cells generate neuroblasts that migrate along the rostral migratory stream to the olfactory bulb, where they differentiate into interneurons and integrate into the existing neural networks
- The process of adult neurogenesis involves several stages, including proliferation, differentiation, migration (rostral migratory stream for SVZ), and integration of newborn neurons into the existing neural circuitry
Functional significance of neurogenesis
Learning and memory
- Adult neurogenesis in the hippocampus plays a crucial role in learning and memory formation, particularly in the context of spatial memory (navigation) and pattern separation (distinguishing similar experiences)
- Newborn neurons in the dentate gyrus exhibit increased excitability and plasticity compared to mature neurons, which may facilitate the encoding of new memories and the discrimination between similar experiences
- Disruption or impairment of adult neurogenesis in the hippocampus has been associated with deficits in learning and memory, suggesting that the continuous generation of new neurons is essential for optimal cognitive function
Mood regulation
- Adult neurogenesis in the hippocampus has also been implicated in the regulation of mood and emotional processing, with reduced neurogenesis being associated with depression and anxiety-like behaviors in animal models
- Antidepressant treatments, such as selective serotonin reuptake inhibitors (SSRIs) (fluoxetine), have been shown to increase adult neurogenesis in the hippocampus, which may contribute to their therapeutic effects on mood disorders
- The functional significance of adult neurogenesis in the olfactory bulb is less clear but may be related to the continuous adaptation to new olfactory experiences (odors) and the maintenance of olfactory memory
Synaptic plasticity for learning and memory
Concept and role
- Synaptic plasticity refers to the ability of synapses to strengthen or weaken in response to changes in neuronal activity or experience, allowing the brain to adapt and modify its neural connections over time
- Synaptic plasticity is a fundamental mechanism underlying learning and memory formation, as it enables the brain to encode, store, and retrieve information by modifying the strength and efficacy of synaptic connections
- Synaptic plasticity is not limited to the hippocampus but occurs throughout various brain regions, contributing to different forms of learning and memory, such as declarative memory (facts and events), procedural memory (skills), and emotional memory (fear conditioning)
Types of synaptic plasticity
- (LTP) is a form of synaptic plasticity that involves the persistent strengthening of synaptic transmission following high-frequency stimulation, leading to enhanced synaptic efficacy and increased postsynaptic response
- (LTD) is another form of synaptic plasticity that involves the persistent weakening of synaptic transmission following low-frequency stimulation or specific patterns of activity, leading to reduced synaptic efficacy and decreased postsynaptic response
- The bidirectional nature of synaptic plasticity (LTP and LTD) allows for the fine-tuning of neural circuits and the formation of specific memory engrams, enabling the brain to store and retrieve information in a precise and context-dependent manner
Mechanisms of synaptic plasticity
Long-term potentiation (LTP)
- LTP is triggered by the activation of postsynaptic NMDA receptors, which are -gated ion channels that allow calcium influx into the postsynaptic neuron when activated
- The calcium influx initiated by NMDA receptor activation leads to the activation of various intracellular signaling cascades, including calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA), which phosphorylate downstream targets and modify synaptic strength
- LTP also involves the insertion of additional AMPA receptors into the postsynaptic membrane, increasing the sensitivity of the postsynaptic neuron to glutamate release and enhancing synaptic transmission
- Structural changes, such as the growth of new dendritic spines and the enlargement of existing spines, are associated with LTP and contribute to the long-term maintenance of
Long-term depression (LTD)
- LTD is triggered by the activation of postsynaptic NMDA receptors at lower frequencies or specific patterns of activity, leading to a moderate calcium influx into the postsynaptic neuron
- The moderate calcium influx during LTD activates protein phosphatases, such as calcineurin and protein phosphatase 1 (PP1), which dephosphorylate downstream targets and reduce synaptic strength
- LTD is associated with the removal of AMPA receptors from the postsynaptic membrane, decreasing the sensitivity of the postsynaptic neuron to glutamate release and reducing synaptic transmission
- Structural changes, such as the shrinkage or elimination of dendritic spines, are associated with LTD and contribute to the long-term maintenance of
Key Terms to Review (18)
Adult neurogenesis: Adult neurogenesis is the process by which new neurons are generated in the adult brain, primarily occurring in the hippocampus. This phenomenon plays a vital role in learning, memory, and mood regulation, as the formation of new neurons contributes to synaptic plasticity, which is essential for adapting neural connections based on experiences and environmental changes.
Age-related decline: Age-related decline refers to the gradual deterioration of cognitive and physiological functions that occurs as individuals grow older. This decline can affect various aspects of brain health, including neurogenesis and synaptic plasticity, leading to decreased learning capacity, memory retention, and overall cognitive flexibility.
Brain-derived neurotrophic factor (bdnf): Brain-derived neurotrophic factor (BDNF) is a crucial protein in the brain that supports the survival, growth, and differentiation of neurons. It plays a vital role in synapse formation, plasticity, and overall brain health. BDNF is involved in guiding axons during development and maintaining neural circuits, while also promoting neurogenesis and enhancing synaptic strength in adults, linking it directly to learning and memory processes.
Cognitive aging: Cognitive aging refers to the gradual decline in cognitive abilities, such as memory, attention, and processing speed, that occurs as individuals grow older. This process affects various aspects of cognition and can impact daily functioning, though many older adults maintain their cognitive abilities into later life. Understanding cognitive aging is crucial for developing strategies to promote mental health and well-being among the aging population.
Depression treatment: Depression treatment refers to the various strategies and interventions designed to alleviate the symptoms of depression and improve overall mental health. These treatments can include psychotherapy, medication, lifestyle changes, and alternative therapies, each targeting different aspects of the disorder. Understanding the connection between depression treatment and neurogenesis and synaptic plasticity is vital, as these biological processes can influence how well an individual responds to treatment and how effective these interventions can be in restoring brain function.
Electrophysiology: Electrophysiology is the study of the electrical properties of biological cells and tissues, focusing on the electrical activities that occur in neurons and muscle cells. This field provides insights into how electrical signals are generated and propagated, which is crucial for understanding cellular communication, neural networks, and muscle contractions.
Environmental Enrichment: Environmental enrichment refers to the process of enhancing an animal's environment by providing various stimuli, resources, and experiences that promote physical, social, and cognitive engagement. This concept is crucial in understanding how enriched environments can positively affect brain function and development, particularly in relation to adult neurogenesis and synaptic plasticity, where increased stimulation can lead to improved learning and memory.
GABA: GABA, or gamma-aminobutyric acid, is the primary inhibitory neurotransmitter in the brain that plays a crucial role in reducing neuronal excitability throughout the nervous system. It helps maintain a balance between excitatory and inhibitory signals, influencing various functions such as mood, motor control, and cognitive processes.
Glutamate: Glutamate is the main excitatory neurotransmitter in the brain, playing a crucial role in sending signals between nerve cells. It's involved in various essential functions including synaptic transmission, plasticity, and learning processes, highlighting its significance across multiple neural pathways and mechanisms.
Hippocampal neurogenesis: Hippocampal neurogenesis is the process by which new neurons are generated in the hippocampus, a brain region crucial for learning and memory. This phenomenon occurs primarily in adulthood and has been linked to various cognitive functions and emotional regulation, highlighting its role in synaptic plasticity and the brain's ability to adapt to new information and experiences.
Hippocampus: The hippocampus is a crucial brain structure located in the medial temporal lobe, primarily involved in the formation and consolidation of new memories and spatial navigation. Its role extends to various cognitive functions, linking it to emotional responses and learning processes.
Immunohistochemistry: Immunohistochemistry is a laboratory technique used to visualize specific proteins or antigens in tissue sections by using antibodies that bind to those targets. This method plays a crucial role in neuroscience by allowing researchers to study the localization and expression of neurotransmitters, receptors, and other important proteins involved in synaptic transmission, axon guidance, synaptic plasticity, and neurogenesis.
Long-term depression: Long-term depression (LTD) is a lasting decrease in the strength of synaptic transmission, occurring when synapses are repeatedly stimulated at a low frequency. This process is crucial for synaptic plasticity, allowing for the weakening of certain synaptic connections while strengthening others, which plays a vital role in learning, memory, and neural circuit refinement.
Long-term potentiation: Long-term potentiation (LTP) is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It plays a crucial role in synaptic transmission and is fundamental for various cognitive functions, including learning and memory, by increasing synaptic strength through biochemical changes.
Neurodegenerative diseases: Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of the structure and function of the nervous system. These conditions lead to the loss of neurons, which can severely impact cognitive functions, motor skills, and overall brain health. Understanding neurodegenerative diseases is crucial for studying adult neurogenesis and synaptic plasticity, as these processes may be altered or impaired in individuals suffering from such conditions, potentially affecting their ability to adapt and recover from neural damage.
Subventricular zone: The subventricular zone (SVZ) is a region in the brain located along the lateral ventricles, known for its role in generating new neurons throughout life. This area is crucial for neurogenesis, particularly in the context of olfactory function and learning, as it contains neural stem cells that can differentiate into various types of neurons and glial cells. The SVZ plays a significant role in both development and adult brain plasticity, contributing to various cognitive processes.
Synaptic strengthening: Synaptic strengthening refers to the process by which synaptic connections between neurons become more effective and efficient in transmitting signals. This increase in synaptic efficacy is a fundamental mechanism underlying learning and memory, as it allows for enhanced communication between neurons, contributing to the formation and maintenance of neural circuits. This process is closely related to synaptic plasticity and plays a critical role in adult neurogenesis by influencing how new neurons integrate into existing neural networks.
Synaptic weakening: Synaptic weakening refers to the process by which synaptic connections between neurons become less effective in transmitting signals. This phenomenon is crucial for maintaining neural circuit balance and is an essential aspect of synaptic plasticity, allowing the nervous system to adjust and refine its neural connections based on experience. Synaptic weakening can occur through various mechanisms, such as long-term depression (LTD), which plays a significant role in learning and memory by facilitating the removal of outdated or less relevant synapses.