Self-Synapsing Cells in the Subiculum
Xingru Pan, Ruoqing Pan, Quansheng He, Wei Ke, and Yousheng Shu
(see article e2301242025)
A subpopulation of neocortical glutamatergic pyramidal cells (PCs) can synapse on themselves. Pan et al. explored whether PCs in the hippocampal formation (HPF) are also able to form functional self-synapses, or autapses. The authors used whole-cell patch-clamp electrophysiology to record autaptic responses from HPF PCs in mice and found that no autapses formed in CA1, CA2, or CA3. However, approximately half of the PCs in the subiculum were able to form autapses. This subpopulation primarily targeted the nucleus accumbens, not the basolateral amygdala. Probing the mechanism of these autaptic responses, Pan and colleagues found that glutamatergic AMPA receptors mediate subiculum autapses earlier in development than autapses in the medial prefrontal cortex. These findings unveil unique autapses in subiculum PCs that develop earlier than neocortical ones.
Distinct Functions of Glutamate Neuron Subtypes in the Midbrain
Dillon J. McGovern, Alysabeth Phillips, Annie Ly, Emily D. Prévost, Lucy Ward et al.
(see article e1073242025)
The ventral tegmental area (VTA) has glutamatergic neurons that support both reward and aversion. These neurons have subpopulations: neurons that release only glutamate, neurons that co-release glutamate and GABA, and neurons that corelease glutamate and dopamine. McGovern and colleagues explored whether these subtypes support reward and aversion differently in mice.
The authors found distinct differences in cellular responses to sweet rewards, caloric (fatty) rewards, and aversive foot shock. Sweeter solutions led to bigger responses in neurons releasing only glutamate or both glutamate and GABA, but the latter also had an increase in sustained activity. Neurons coreleasing glutamate and dopamine only increased sustained activity in response to sweeter solutions. Probing differences in sweet versus fatty reward intake, neurons coreleasing glutamate and GABA signaled more for sweet solutions over fatty ones, while the other two subtypes signaled more for high-fat solutions. Assessing the role of each subpopulation in unpleasant states, McGovern et al. found that foot shock increased activity of all cell types, though neurons coreleasing glutamate and GABA had more uniquely altered activity. When the authors used optogenetics to artificially activate neurons coreleasing glutamate and GABA during low intensity foot shock, this promoted fear behavior. Lastly, approximately half of the neurons coreleasing glutamate and GABA with sensitivity to sweet solutions were also activated by footshock. According to the authors, this study lays the groundwork for probing the roles of VTA glutamatergic neuron subtypes in reward and aversion.
VTA section expressing mKate (red), GFP (green), and c-Fos (blue). Approximately half of the VTA sucrose-activated neurons that corelease glutamate and GABA were also activated by foot shock, most within the interfascicular nucleus. See McGovern et al. for more information.
Footnotes
This Week in The Journal was written by Paige McKeon
