One of the most remarkable features of dendritic BI-D1870 spines is their morphological diversity. The three categories studied here appear to have different functional properties, including activity induced changes in intracellular calcium concentration, glutamate receptor levels and perhaps new versus well established memory processing. Additionally, dendritic spine morphology has also been reported to affect the diffusion and compartmentalization of membrane associated proteins and expression of a-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Given this information, we assessed whether the proportions of each type of spine were altered in the DG and CA1 area following radiation exposure. Our data showed that in both DG and CA1 basal dendrites, spines characterized by the mushroom morphology were particularly affected by radiation exposure. Mushroom spines have larger postsynaptic densities which anchor more AMPA glutamate receptors and make these synapses functionally stronger. Mushroom spines are more likely to contain smooth endoplasmic reticulum, which can regulate calcium locally and spines that have larger synapses are also more likely to contain polyribosomes for local protein synthesis. Thus, the loss of mushroom spines as seen here may have a more profound effect on neuronal function than the loss of the other types of spines. Gao et al has also recently reported that moderate traumatic brain injury in mice led to significant decrease in mushroom shaped spines indicating a reduction in number of synapses which was confirmed by synaptophysin staining. Whereas radiation exposure led to decrease in the fraction of mushroom spines, a marked increase in the proportion of stubby spines were observed in both DG and CA1 basal dendrites 1 month post irradiation. Although less is known about these stubby structures, they have been shown to predominate early in postnatal development and to increase in mature hippocampal slices after synaptic transmission was blocked. It has also been reported that dopamine receptors are located on the spine neck in the perisynaptic space and stubby spines that lack a neck likely have abnormal distributions of dopamine receptors in this space. It can be speculated that a marked increase in the proportion of stubby spines by radiation exposure might therefore lead to some alterations in dopaminergic signaling. Because radiation has been reported to affect dopaminergic processes in the brain, such changes may have long-term consequences for radiation induced cognitive changes. Despite the fact that no change in spine density was observed in the apical dendrites of CA1 neurons after irradiation, significant differences in thin and mushroom spine morphology were observed between the sham and irradiated groups. It is noteworthy that contrary to what was observed in DG and CA1 basal dendrites, irradiation led to significant decreases in the percentages of thin spines after irradiation and a significant increase in mushroom spines. The length of the spine neck seems to be a key regulator of spinodendritic Ca2+ signaling and of the transmission of membrane potentials. Thin spines maintain the structural flexibility to enlarge and stabilize after long term potentiation and can accommodate new, enhanced or recently weakened inputs, making them candidate ‘learning spines’. By decreasing the proportion of learning spines, radiation may therefore decrease a neuron’s ability to form new synapses and changes in activity in the CA1 apical dendrites. Age related reductions in thin spines have been observed in rhesus monkeys, with cognitive performance inversely proportional to thin spine volume.