This Week in The Journal

Dendritic Spines Need ßIII Spectrin

Nadia Efimova, Farida Korobova, Michael C. Stankewich, Andrew H. Moberly, Donna B. Stolz, et al.

Dendritic spines come in a variety of shapes, including long and thin, short and stubby, and mushroom-shaped, with a thin stalk and large head. Spine shape is thought to influence the movement of ions and proteins between spine synapses and the dendritic shaft, and thus affect excitatory transmission. Several neurological conditions, including intellectual disability, autism, and Alzheimer's disease are associated with changes in the number and/or shape of dendritic spines, but whether differently shaped spines serve different functions or simply reflect different stages of spine development is unclear. Moreover, how spine shape is regulated is poorly understood.

One potential regulator of spine shape is ßIII spectrin. Spectrins crosslink actin filaments, helping to form the actin meshwork underlying the plasma membrane. They also bind numerous other proteins, including ion channels, glutamate transporters, and cell adhesion molecules. Mutations in ßIII spectrin cause spinal cerebellar ataxia type 5, characterized by loss of Purkinje cell spines and dendrites. ßIII spectrin mutations also cause spectrin-associated autosomal recessive cerebellar ataxia type 1, which causes cognitive symptoms as well as ataxia.

Efimova et al. report that ßIII spectrin is expressed in the hippocampus and cortex, as well as cerebellum, and expression increases in parallel with spine development in cultured hippocampal neurons. In mature neurons, ßIII spectrin was highest in the base and necks of spines, and thus it did not colocalize with the postsynaptic density protein PSD-95. Notably, knocking down ßIII spectrin reduced the density of dendritic spines in cultured hippocampal and cortical neurons. It also reduced the density of PSD-95 puncta, and often shifted the remaining puncta from spines to dendritic shafts. Moreover, while the density of synapsin-expressing presynaptic terminals was unaffected by ßIII spectrin knockdown, these puncta were often apposed to dendritic shafts instead of spines. Finally, ßIII spectrin knockdown resulted in an increase in amplitude, but not frequency of miniature EPSCs.

Together, these results suggest that ßIII spectrin is necessary for formation and/or maintenance of dendritic spine necks, and thus for limiting EPSC amplitude. Therefore, excitotoxicity may contribute to the neurological consequences of ßIII spectrin mutations. Future work should determine what proteins interact with ßIII spectrin to maintain dendritic spines and promote localization of PSD-95.

Suppressing Memories Suppresses Associated Emotions

Pierre Gagnepain, Justin Hulbert, and Michael C. Anderson

(see pages 6423–6441)

People sometimes encounter stimuli that remind them of unpleasant past events that they would rather not recall. When such memories intrude, most people can suppress them by clearing their minds or thinking of something else. This ability, which resembles motor response inhibition, is mediated by prefrontal cortical areas that inhibit retrieval networks in the hippocampus. Interestingly, repeated suppression of memories promotes forgetting, making the memories less likely to be recalled in the future. Moreover, suppression of unpleasant memories appears to reduce their negative valence. Whether this results from direct suppression of affective processing or indirectly, from weakening the memory trace, has been unclear. Gagnepain et al. now provide evidence favoring the former hypothesis.

Brain areas that were more active (warm colors) or less active (cool colors) when participants suppressed memories than when they retrieved memories. See Gagnepain et al. for details.

In their study, people learned to associate face images with unpleasant or neutral scenes; then, while undergoing functional magnetic resonance imaging, participants were shown faces and asked to recall or suppress memories of the associated scene. On each “suppress” trial, subjects rated the effectiveness of the suppression. After scanning, subjects' memory for each face–scene association was tested, and they were asked to rate the unpleasantness of each scene.

Consistent with previous work, most subjects' ability to suppress recall increased with repetition, and successful suppression slowed recall of suppressed scenes relative to unsuppressed scenes. In addition, successful suppression was associated with less negative ratings of unpleasant scenes. In further agreement with previous work, suppressing recall was linked to activation of a broad area of right dorsolateral prefrontal cortex, including the middle frontal gyrus (MFG), and reduced activation in hippocampus. Amygdala activation was also reduced on “suppress” trials, but only those involving unpleasant scenes. Further analyses suggested that the same MFG regions were involved in both mnemonic and emotional suppression, and that the hippocampus and amygdala were inhibited in parallel during suppression of unpleasant scenes.

These results suggest that MFG suppresses intrusive, unpleasant memories by reducing activity in both the hippocampus and the amygdala. Note that this effect of MFG is likely indirect, however. The results also confirm that memory suppression not only inhibits future recall, but also reduces emotional valence. Improving people's ability to suppress intrusive memories may therefore be helpful in treating posttraumatic stress disorder and other psychological conditions involving intrusive memories.