Search

Dopaminergic neurons originating from the ventral tegmental area (VTA) and the locus coeruleus are innervating the ventral hippocampus and are thought to play an essential role for efficient cognitive function. Moreover, these VTA projections are hypothesized to be part of a functional loop, in which dopamine regulates memory storage. It is hypothesized that when a novel stimulus is encountered and recognized as novel, increased dopamine activity in the hippocampus induces long-term potentiation and long-term storage of memories. We here demonstrate the importance of increased release of dopamine and norepinephrinein the rat ventral hippocampus on recognition memory, using microdialysis combined to a modified novel object recognition test. We found that presenting rats to a novel object significantly increased dopamine and norepinephrine output in the ventral hippocampus. Two hours after introducing the first object, a second object (either novel or familiar) was placed in the same position as the first object. Presenting the animals to a second novel object significantly increased dopamine and norepinephrine release in the ventral hippocampus, compared to a familiar object. In conclusion, this study suggests that dopamine and norepinephrine output in the ventral hippocampus has a crucial role in recognition memory and signals novelty., De två sista författarna delar sistaförfattarskapet.

Despite their low abundance, telencephalic interneurons demonstrate a great amount of molecular and electrophysiological heterogeneity, suggesting that they exhibit different functions within the circuit. Interneurons are commonly classified into distinct cell types based on their morphology, intrinsic electrophysiological properties, connectivity or molecular profile. However, it is only when combining knowledge about the aforementioned parameters that appropriate classification of cellular and circuit function can be achieved. In Paper I, we characterized the molecular and electrophysiological diversity of striatal interneurons, either using single-cell-RNA-seq (scRNA-seq) alone or in combination with whole-cell ex-vivo electrophysiological recordings (PatchSeq). Interestingly, unlike in other regions of the brain, striatal Pvalb-expressing cells did not constitute a discrete cluster, but was instead part of the larger group labeled with the gene Pthlh. Using PatchSeq, we were able to show that gradient-like differences in gene expression found within the Pthlh group, correlate with a continuum of electrophysiological properties. In Paper IV, we show that more stable readouts such as anatomical location, morphology, and long-range inputs also gradually differ across this molecular and electrophysiological continuum. Hence, we suggest that separate parts of this gradient exhibit a distinct circuit function. Upon long-term activation of the Pthlh population, we detected an increase in Pvalb expression within the most ventral part of the striatum. Thus, the gradient-like differences in gene expression that we observed within the Pthlh population could be caused by long-term changes in activity upon altered input. In Paper II, the molecular diversity of hippocampal CA1 interneurons was characterized using scRNA-seq. While the main clusters were clearly separated, similar to the findings of Paper I, many sub-clusters exhibited more of a continuum within the continents.