The distribution of inhibitory spine synapses may also relate to the different sources of excitatory connections onto the apical dendrite, suggesting they may be involved in gating specific types of inputs. The apical tuft of L2/3 pyramidal
neurons receives a larger proportion of excitatory inputs Ulixertinib from more distant cortical and subcortical locations compared to other parts of the dendritic arbor (Spruston, 2008). Subcortical afferents have been identified as the excitatory input that co-innervates spines with inhibitory synapses (Kubota et al., 2007), suggesting that these inhibitory contacts are ideally situated to directly modulate feed-forward sensory-evoked activity in the cortex. Interestingly, we find that all of these co-innervated spines are stable, both during normal experience and MD, regardless of the dynamics of the inhibitory spine synapse. This suggests that subcortical inputs entering the cortex onto dually innervated spines are likely to be directly gated by inhibition at their entry level, the spine, but because of the structural stability of these
feed forward inputs, their functional modification would have to rely on removal/addition of the gating inhibitory input. This particular type of excitatory synapse may be much more directly influenced click here by the inhibitory network than excitatory synapses on singly innervated spines that are exposed to the inhibitory network only at the level of the dendrite. Inhibitory synapses are quite responsive to changes in sensory experience. Recently, focal retinal lesions have been shown to produce large and persistent losses in axonal boutons in the adult mouse visual cortex (Keck et al., 2011). Our ability to distinguish inhibitory spine and shaft synapses provide insight into the degree of inhibitory synapse dynamics
in the adult visual cortex. We find that in binocular visual cortex, MD produces a relatively large initial increase in inhibitory spine synapse loss. Acute changes in inhibitory spine synapse density have also been observed in the barrel cortex after 24 hr of whisker stimulation PD184352 (CI-1040) (Knott et al., 2002), further supporting the notion that these synapses are highly responsive and well suited to modulate feed-forward sensory-evoked activity. Whereas inhibitory spine synapses are responsive to the initial loss of sensory input, the sustained increase in inhibitory shaft synapse loss we observe parallels the persistent absence of deprived-eye input and may serve the broader purpose of maintaining levels of dendritic activity and excitability during situations of reduced synaptic drive. These losses in inhibitory synapses are consistent with findings that visual deprivation produces a period of disinhibition in adult visual cortex (Chen et al., 2011, He et al., 2006, Hendry and Jones, 1986 and Keck et al., 2011) that is permissive for subsequent plasticity (Chen et al., 2011, Harauzov et al.