B) Electron micrograph showing a dendrite (D) with two spines (S). Each spine receives an … The functional integrity of the pyramidal Tanespimycin neurons with lower dendritic spine densities may be reflected in changes in their somal volume. For example, shifts in somal size may indicate disturbances in neuronal connectivity, given that somal size has been shown to be correlated with measures of a neuron’s dendritic tree28 and axonal arbor.29 Indeed, the mean cross-sectional

somal area of the Golgi-impregnated, deep layer 3 pyramidal neurons was 9% smaller in the subjects with schizophrenia relative to normal control subjects.25 Consistent with this observation, the mean somal Inhibitors,research,lifescience,medical volume of Nisslstained pyramidal Inhibitors,research,lifescience,medical neurons in DLPFC deep layer 3 was also 9% smaller in a different cohort of subjects with schizophrenia.30 Similarly, in another study, the mean somal size of all layer 3 neurons in DLPFC area 9 was smaller in subjects with schizophrenia, and was accompanied by a decrease in the density of the largest neurons in deep layer 3, without a change in somal volume in layer 5.31 Furthermore, in both primary and association auditory cortices, somal volumes of deep layer 3, but not of layer 5, pyramidal neurons were smaller in schizophrenia.32,33 Together, these findings suggest that in schizophrenia: i) basilar Inhibitors,research,lifescience,medical dendritic spine

density is lower and somal volume is smaller in deep layer 3 pyramidal neurons; ii) these alterations are specific to or at least most prominent in deep layer 3; iii) this pattern of alterations Inhibitors,research,lifescience,medical is not restricted to the DLPFC; and iv) these differences reflect the underlying

disease process and not confounding factors. The contribution of developmental plasticity to dendritic spine alterations in schizophrenia Dendritic spine density on DLPFC layer 3 pyramidal neurons undergoes a substantial decline during adolescence in primates.34 Consistent with the findings that dendritic spines are the main site of excitatory synaptic input onto Inhibitors,research,lifescience,medical pyramidal cells and that all mature dendritic spines contain an excitatory synapse,35 the number of excitatory synapses declines in a similar age-related fashion in both monkey and human DLPFC.36,37 In humans, this synaptic pruning is thought to underlie the decrease in cortical gray matter thickness that occurs during adolescence.38,39 Interestingly, the late developmental refinements in excitatory connectivity Bay 11-7085 are more marked in layer 3 than in the deeper cortical layers,36 suggesting that they may be associated with the apparent laminas-specific alterations in spine density in schizophrenia. The observation of alterations in the expression of certain synaptic proteins in schizophrenia suggested the possibility that the exuberant synapses present before adolescence somehow compensated for a dysfunction in excitatory transmission in individuals with schizophrenia.