The spatial distribution of inputs from an axon onto its target plays a key role in the way information is integrated by the postsynaptic neuron. Although much is known about the physiological

and pharmacological properties of the powerful synapse made by thalamic axons onto cortical inhibitory interneurons (Cruikshank et al., 2007, Gabernet et al., 2005, Anti-diabetic Compound Library Gibson et al., 1999 and Hull et al., 2009), the spatial organization of this input is unknown. Through Ca imaging we revealed that the contact sites (hotspots) of individual thalamic inputs are located on the proximal dendrites of L4 interneurons, preferentially near branch points. Each hotspot represents a single synaptic bouton capable of releasing up to seven vesicles simultaneously, and each thalamic axon forms a variable number of these boutons spread across the dendrites of individual cortical interneurons, depending on the strength of the input. This structure of many spatially

Selleck IWR-1 separated synapses, each capable of multivesicular release, as schematically illustrated in Figure 1C, may have consequences for how sensory information is transmitted to cortical interneurons, because it promotes locally reliable and graded Ca transients while minimizing the inefficiencies of clustered release sites. Through such clusters, the spatial representation of thalamic sensory inputs onto the dendritic arbor is faithfully reproduced, spike after spike. Histological analyses revealed that hotspots were predominantly located on proximal dendrites, 95% occurring in the first 115 μm (Figure 8), consistent with ultrastructural studies (Ahmed et al., 1997, White et al., 1984 and White and Rock, 1981). Together with structural data showing that ∼15% of thalamic inputs to interneurons may be axosomatic (Ahmed et al., 1997 and Staiger et al., 1996), and recent findings suggesting a similar

proximal bias for thalamic inputs onto cortical excitatory neurons (Richardson et al., 2009), our data highlight one of the key parameters first likely to contribute to the relative strength of thalamocortical inputs despite their numerical sparseness (Gil et al., 1999 and Stratford et al., 1996). Synaptic contacts of a single axon were distributed on the dendrites independent of each other’s location indicating the lack of dedicated dendritic domains (Figure 8) (Bollmann and Engert, 2009, Jia et al., 2010, Peron et al., 2009 and Petersen et al., 2008). Furthermore, hotspots from the same axon were not located at similar distance from the soma as each other, suggesting the absence of an axon-specific uniform electrotonic distribution and consistent with the lack of correlation between the location of individual hotspots and the amplitude of the associated uEPSC (Figure 8A).