e., enhanced expression of GluA2-containing AMPARs) with far slower kinetics (>12 hr; Turrigiano et al., 1998, Wierenga et al., 2005 and Sutton et al., 2006). This notion is further supported by the observation that spatially restricted blockade of NMDAR miniature events enhances surface GluA1 expression locally ( Sutton et al., 2006). Although these observations and some theoretical considerations ( Rabinowitch and Segev, 2008) argue for a local homeostatic mechanism, there is also check details strong evidence for more global homeostatic control mechanisms in neurons that may be tuned to firing rate

( Turrigiano et al., 1998). There are unique theoretical advantages of global homeostatic mechanisms as well, particularly with regard to preserving information coding capabilities of neurons ( Turrigiano, 2008). A recent study directly assessed the impact of blocking postsynaptic firing by confining TTX treatment to the postsynaptic

cell body. Ibata et al. (2008) found such somatic AP blockade induced a transcription-dependent accumulation of GFP-tagged GluA2 at multiple sites throughout the dendritic arbor remote from the perfusion site, indicative of a cell-wide homeostatic mechanism. This transcription-dependent connection adds an interesting parallel with other evidence implicating the immediate early Fulvestrant order gene Arc in global homeostatic control ( Shepherd et al., 2006) and also distinguishes this global mechanism

with transcription-independent synaptic insertion of GluA2-lacking receptors that accompanies mini blockade ( Aoto et al., 2008). Taken together, these observations support the existence of multiple modes of homeostatic control in neurons Idoxuridine that are mediated by separate molecular pathways and implemented over distinct spatial scales. Since the discovery of polyribosomes beneath synaptic sites on dendrites, the hypothesis that dendritic protein synthesis can be engaged to adjust synaptic composition on a local level has received considerable attention. Our results indicate that in addition to allowing for fine spatial control over the postsynaptic element, local dendritic synthesis may also actively participate in controlling the function of apposed presynaptic terminals, through local synthesis of BDNF and perhaps other retrograde messengers. Thus, BDNF is both necessary and sufficient for the state-dependent presynaptic changes induced by AMPAR blockade, but acts downstream of protein synthesis. Furthermore, AMPAR blockade enhances dendritic BDNF expression in a translation-dependent manner, and a local decrease in dendritic BDNF expression accompanies spatially restricted inhibition of dendritic protein synthesis when performed coincident with AMPAR blockade.