Heterosynaptic plasticity may play an important
homeostatic role in neural plasticity by normalizing or limiting the total change of synaptic input during ongoing
Hebbian plasticity. Hebbian plasticity, an ubiquitous form of homosynaptic, associative plasticity, is believed to underlie learning and memory. Moreover, Hebbian plasticity is induced by and amplifies correlations in neural circuits which creates a positive feedback loop and renders neural circuits unstable. To avoid too much instability Hebbian plasticity needs to be constrained, for instance by the conservation of the total amount of synaptic input. This role is believed to be fulfilled by a diversity of homeostatic mechanisms. However, to effectively stabilize Hebbian plasticity, which can be induced in a matter of seconds to minutes, homeostatic plasticity has to react rapidly. This requirement, however, is not met by most forms of homeostatic plasticity, which typically act on timescales of hours, days or longer. This limitation does not seem to apply to heterosynaptic plasticity. To achieve a homeostatic effect, and limit synapse instability, heterosynaptic plasticity serves its homeostatic role through pathway unspecific synaptic changes in the opposite direction of Hebbian plasticity. In other words, whenever homosynaptic
long-term potentiation is induced at a given synapse, other unstimulated synapses should be depressed. Conversely, homosynaptic
long-term depression would cause other synapses to potentiate in a manner which keeps the average
synaptic weight approximately conserved. The scope of these changes could be global or compartmentalized in the
dendrites. This theory of balancing the approximate dendritic activity locally, was proposed by Rabinowitch and Segev, and has been further exemplified by hippocampal neurons and neurons in the
amygdala.
Developmental Plasticity The development of neurons, specifically synapses from those almost entirely lacking vesicles pre-synaptically, and forming tight junctions with other neurons, to adult, chemical transmitting capable neurons, is a very long process executed by many biological functions, including contributions by plasticity. Early in development, synaptic connections are not input-specific, most likely because of Ca2+ spillover (i.e. Ca2+ is not restricted to dendrites specifically activated). This spillover represents another mechanism of heterosynaptic change in plasticity. Networks are later refined by input-specific plasticity, which allows for the elimination of connections that are not specifically stimulated. As neuronal circuits mature, it is likely that the concentration of Ca2+ binding proteins increases, which prevents Ca2+ from diffusing to other sites. Increases in localized Ca2+ lead to AMPARs inserted into the membrane. This increase in AMPA density in the postsynaptic membrane increases enables NMDARs to be functional, allowing more Ca2+ to enter the cell. NMDAR subunits also change as neurons mature, increasing the receptor's
conductance property. These mechanisms facilitate Ca2+ location restriction, and thus specificity, as an organism progresses through development. In addition to Ca2+ specific mechanisms, increasing total numbers of vesicles in the vesicle pool and extended
action potential duration, in young organisms may contribute to observed changes in the same neurons at different ages. For example, studies of the stimulation of MNTB (Medial Nucleus of Trapezoid Body) neurons at a young age has been shown to create a short term depressive effect, however when repeated in mature MNTB neurons, this is not the case. Further possible mechanisms accounting for changes such as in the previous example, may be the alteration of depolarization and
hyperpolarization amplitudes throughout development. For example, hyperpolarizing neurons producing
Inhibitory Post Synaptic Potentials (IPSPs), became more hyperpolarized throughout development reaching more negative
membrane potential values. RAI1 influences synaptic scaling indirectly because it regulates gene expression in neurons, including genes involved in synaptic function and neuronal activity. Synaptic scaling depends on proper expression of proteins that adjust synaptic strength up or down to keep neural activity stable. When RAI1 (Retinoic Acid Induced 1) is reduced, this gene regulation is disrupted, which can affect the neuron's ability to maintain that balance and properly carry out homeostatic synaptic scaling NRP2 is involved in pathways that help regulate homeostatic synaptic scaling, which is the process neurons use to keep their activity stable by strengthening or weakening all synapses. When NRP2 (neuropilin-2) activity is reduced, it can lessen signals that promote synaptic downscaling (reducing synaptic strength), allowing synapses to remain stronger and improving neural communication. Decreased NRP2 after exercise may have supported a healthier balance of synaptic activity, making it easier for neurons to maintain stable firing while still adapting and learning. ==References==