Neural Plasticity

Review Article

Wherefore Art Thou, Homeo(stasis)? Functional Diversity in Homeostatic Synaptic Plasticity

Table 2

Inactivity paradigms: consequences and responses. Inactivity paradigms are grouped by scope: network-wide, cell autonomous, or synapse specific. Each inactivity paradigm is evaluated based on its type: presynaptic (Pre) or postsynaptic (Post) mode of action, and reduction (↓) or elimination (X) of activity.


Paradigm type			Synaptic/cellular consequences	Perceived situation	Cell autonomous response

Network-wide inactivity

TTX	Pre	↓	Developing network: fewer presynaptic inputs; no emergence of AP firing to constrain synapses	Participation in a sparsely connected network	Calibration of synaptic strength to higher level [26, 38, 59] via constitutive insertion of somatically synthesized GluA1/2 AMPARs [34]
			Established network: Sudden decrease in output with concurrent decrease in presynaptic inputs	Change in network activity state	Compensation via insertion of somatically synthesized GluA1/2 AMPARs [34] with possible coordination of presynaptic properties (↑ release probability or # synaptic vesicles) or potential ↑ # synaptic sites

APV	Post	↓	Diminished Ca²⁺ influx at synapses	Disrupted synaptic Ca²⁺ homeostasis	Minimal effect at AMPARs [38]

TTX+ APV	Post	↓↓	Sudden decrease in output with concurrent decrease in presynaptic inputs, and diminished synaptic Ca²⁺	Change in network activity state, disrupted synaptic Ca²⁺ homeostasis	Homeostatic compensation via rapid insertion of locally synthesized Ca²⁺ permeable homomeric GluA1 AMPARs [35]

NBQX	Post	X	Sudden decrease in postsynaptic efficacy at an otherwise functional synapse	Disrupted synaptic function and synaptic Ca²⁺ homeostasis	Homeostatic compensation via increase in presynaptic release probability and rapid insertion of locally synthesized Ca²⁺ permeable homomeric GluA1 AMPARs [24, 51]

Cell-autonomous inactivity

Kir2.1	Post	↓	Developing network: less action potential firing than neighbors; less activity-dependent strengthening of synaptic connections	Participation in an “irrelevant” circuit	Inability to compete for synaptic connections in an activity-dependent fashion; lower levels of AMPAR input; lower frequency of inputs (note: this “competition” effect is reversed by global TTX which equalizes activity across the network [45])
			Established network: gradual decrease in output without decrease in presynaptic inputs	Decreased postsynaptic efficacy	Homeostatic compensation via increase in presynaptic release probability [45]

Synapse-specific inactivity

Kir2.1	Pre	↓	Diminished presynaptic input in a normally functioning network	Decreased presynaptic efficacy	Homeostatic compensation via insertion of GluA1 AMPARs [47]

TeTx	Pre	X	Absent presynaptic input in a normally functioning network	Nonfunctional presynaptic terminal	Lack of activity-induced maintenance of GluR1 via diffusional trapping [75]; loss of GluR1 but not GluR2/3 or synaptic proteins [76]

Inactivity paradigms: AP blockade (TTX); NMDAR blockade (APV); AMPAR blockade (NBQX); hyperpolarization (via transfection of Kir2.1 potassium channel); presynaptic release inhibition (via transfection of tetanus toxin, TeTx).