Morphologic evidence for spatially clustered spines in apical dendrites of monkey neocortical pyramidal cells

Abstract

The general organization of neocortical connectivity in rhesus monkey is relatively well understood. However, mounting evidence points to an organizing principle that involves clustered synapses at the level of individual dendrites. Several synaptic plasticity studies have reported cooperative interaction between neighboring synapses on a given dendritic branch, which may potentially induce synapse clusters. Additionally, theoretical models have predicted that such cooperativity is advantageous, in that it greatly enhances a neuron’s computational repertoire. However, largely because of the lack of sufficient morphologic data, the existence of clustered synapses in neurons on a global scale has never been established. The majority of excitatory synapses are found within dendritic spines. In this study, we demonstrate that spine clusters do exist on pyramidal neurons by analyzing the three-dimensional locations of ~40,000 spines on 280 apical dendritic branches in layer III of the rhesus monkey prefrontal cortex. By using clustering algorithms and Monte Carlo simulations, we quantify the probability that the observed extent of clustering does not occur randomly. This provides a measure that tests for spine clustering on a global scale, whenever high-resolution morphologic data are available. Here we demonstrate that spine clusters occur significantly more frequently than expected by pure chance and that spine clustering is concentrated in apical terminal branches. These findings indicate that spine clustering is driven by systematic biological processes. We also found that mushroom-shaped and stubby spines are predominant in clusters on dendritic segments that display prolific clustering, independently supporting a causal link between spine morphology and synaptic clustering.

Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans

“…Dendrites regulate the integration of inputs and provide sites for synapses on spines (41, 42). As such, they are extremely plastic structures that undergo changes in response to experience, which is especially evident during development (12,(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57). For this reason, a delay in the formation of dendritic trees in the prefrontal cortex may be important for processing and integrating the extensive load of information that both humans and chimpanzees acquire during development and for maintaining plasticity of executive functions.…”

Synaptic clustering within dendrites: An emerging theory of memory formation

“…Anatomical clustering has also been documented in the primate cortex (Yadav et al, 2012). Analysis of the locations of spines in the prefrontal cortex of rhesus monkeys confirmed the preference for spatial spine clustering.…”

“…As detailed in section 2.4., an increasing number of studies have shown that synaptic contacts can group together within a short stretch of the dendritic branch, forming anatomical clusters 2 (Makino & Malinow, 2011; Yadav et al, 2012) and/or create functional clusters whereby several neighboring synapses are activated synchronously (Fu, Yu, Lu, & Zuo, 2012; Kleindienst, Winnubst, Roth-Alpermann, Bonhoeffer, & Lohmann, 2011; Takahashi et al, 2012), in the absence of obvious spine density changes This patterned spatial synaptic arrangement along with concrete evidence of dendritic spike generation both in vitro (Ariav et al, 2003; Häusser et al, 2000; S. Kim et al, 2012; Larkum & Nevian, 2008; Losonczy & Magee, 2006; Makara & Magee, 2013; Nevian et al, 2007; Schiller et al, 2000a) and in vivo (Lavzin et al, 2012; Major et al, 2013; S.…”

“…As the study of dendrites is an active area of research, our knowledge of dendritic function and synaptic plasticity is only partially complete. For example, both the size and the spatial extent of functional and/or anatomical dendritic synapse clusters can only be inferred with imaging methods such as calcium imaging, immunolabeling or electron microscopy (Kleindienst et al, 2011; Makino & Malinow, 2011; Takahashi et al, 2012; Yadav et al, 2012). Similarly, the temporal constraints related to synaptic capture, plasticity protein production and homeostatic mechanisms can be found in relevant studies (Govindarajan et al, 2011; Hou et al, 2011; Losonczy et al, 2008).…”

Synaptic competition in structural plasticity and cognitive function

“…Indeed, Yadav et al [33] found that anatomical spine clusters (groups of three or more) occur significantly more frequently than chance within apical dendrites of layer III cells of the monkey prefrontal cortex. This study reveals the capability of neurons to spatially organize spines, but it does not prove a causal relationship between functional and structural changes.…”