Where No Synapses Go: Gatekeepers of Circuit Remodeling and Synaptic Strength

Trends Neurosci, 2013 · DOI: 10.1016/j.tins.2013.04.003 · Published: June 1, 2013

Regenerative Medicine Neurology Genetics

Simple Explanation

Growth inhibitory molecules, traditionally known for blocking axonal regeneration after injury, also play roles in regulating synaptic plasticity and stability in the healthy adult brain. These molecules, including Nogo-A, OMgp, and CSPGs, target the neuronal actin cytoskeleton to influence dendritic spine maturation and long-term synapse stability. Dysfunction of these inhibitors is linked to mental illness and memory loss, highlighting their importance in maintaining brain health beyond just preventing axonal regrowth.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
CNS regeneration inhibitors like Nogo-A and CSPGs promote dendritic spine maturation and stability, influencing neuronal structure in a cell-autonomous manner.
2
NgR1, NgR2, and NgR3 inhibit the formation of excitatory synapses, acting as 'anti-synaptogenic' factors that counterbalance synapse formation.
3
Nogo-A, OMgp, and NgR1 regulate activity-dependent synaptic strength by antagonizing plasticity-promoting signaling pathways activated by neurotrophic factors like FGF2 and BDNF.

Research Summary

CNS regeneration inhibitors, including Nogo-A, OMgp, and CSPGs, have novel functions in regulating dendritic spine maturation, synapse stability, and synaptic plasticity in the naïve CNS. These inhibitors act as gatekeepers of circuit remodeling by targeting the neuronal actin cytoskeleton and antagonizing plasticity-promoting signaling pathways. Dysregulation of these molecules is implicated in mental illness and memory loss, suggesting their critical role in maintaining brain health and long-term network stability.

Practical Implications

Therapeutic Potential

Modulating CNS regeneration inhibitors could offer therapeutic opportunities for CNS injuries, mental illnesses, or memory disorders.

Rehabilitation Strategies

Combining manipulation of CNS inhibitors with task-specific rehabilitation may maximize behavioral outcomes following stroke or other CNS injuries.

Understanding Brain Disorders

Detailed knowledge of these molecular programs could provide insights into the dysregulation of synaptic processes in neurological disorders like schizophrenia and autism.

Study Limitations

1
The precise receptor mechanisms governing dendritic and axonal functions of Nogo-A, OMgp, and CSPGs are incompletely understood.
2
The functional significance of the interaction between NgR1 and NgR3 with CSPGs and HSPGs in the axonal and dendritic compartments of naïve CNS neurons needs further exploration.
3
The extent to which the plethora of known CNS regeneration inhibitors exert similar functions in protecting memory and whether they can be targeted therapeutically without impairing vital neurologic functions remains an open question.

Your Feedback

Was this summary helpful?

Back to Regenerative Medicine