Pictured above: Figure 2 from the article, "Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer’s Disease Entorhinal Cortex," highlighted below.
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READ THE CURRENT ISSUE OF IBRO Neuroscience (vol. 372) published on 21 February 2018.
Highlights from this issue include:
In this issue, Murray et al. ("Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer’s Disease Entorhinal Cortex"), using immunohistochemical techniques and confocal microscopy, convincingly confirm previous evidence of the presence of PSA-NCAM-expressing interneurons in the adult human brain. They describe their distribution and neurochemical phenotype in different regions of the hippocampal formation, the entorhinal cortex and the neocortex. These results are interesting because in these inhibitory neurons the presence of PSA-NCAM appears to have an insulating role, limiting the membrane space available for synaptic contacts (Gomez-Climent et al., 2011). The authors also report a decrease in the number of these PSA-NCAM-expressing interneurons in the entorhinal cortex of Alzheimer’s disease patients. The decrease is particularly evident in the subpopulation of parvalbumin-expressing interneurons. This result is particularly interesting because recent studies have shown that the structure and connectivity of mature interneurons is regulated by PSA-NCAM (Nacher et al., 2013). Particularly, the expression of this molecule is a critical regulator of the perisomatic innervation of cortical pyramidal neurons by parvalbumin-expressing basket cells (Castillo-Gómez et al., 2011). The results of the study by Murray et al. are also interesting because interneurons, and specially basket cells, are important modulators of the synchrony and oscillatory activity of cortical circuits. These parameters controlled by interneurons are crucial for cognitive phenomena and appear to be altered even before the appearance of clinical symptoms in Alzheimer’s disease (Palop and Mucke, 2016). Although more detailed analyses should be performed in the future, both in humans and in animal models, the alterations observed in the interneuronal expression of PSA-NCAM in Alzheimer’s disease may well indicate changes in their connectivity and therefore in their control of the neuronal networks, which may contribute to cognitive decline.
In this volume, the optogenetics paper from Fishbach-Weiss, Reese, and Janak ("Inhibiting Mesolimbic Dopamine Neurons Reduces the Initiation and Maintenance of Instrumental Responding") reports novel and important findings on the behavioral effects of specific inactivation of ventral tegmental area (VTA) DA neurons. Optogenetic inhibition of VTA tyrosine hydroxylase-positive neurons was employed to probe the role of DA neuron activity during instrumental responding for food reinforcement by varying the time points during which neural inhibition was implemented relative to the onset of response initiation. Mice were tested on either a fixed ratio schedule requiring 8 nose poke responses for food delivery, or a progressive ratio schedule (i.e., the ratio requirement increased during the session). In either case, inhibiting DA neurons while mice were not responding decreased the probability of initiating an instrumental response, but had no effect on the total amount of effort exerted across the session. Furthermore, inhibiting DA neurons during the period in which mice were engaged in response bouts decreased the tendency to continue responding. If DA neuron inhibition was initiated during each attempted bout, total responding was suppressed, which thus reduced the total amount of food obtained. In contrast, when inhibition was applied only during some response bouts, mice compensated by increasing the number of bouts initiated when inhibition was not being applied, which resulted in levels of reinforcement that were comparable to those obtained under control conditions. Based upon these results, the authors concluded that VTA DA signaling promotes the initiation of instrumental responding, and also facilitates the motivation to maintain ongoing bouts of effortful instrumental responses. These findings are important for several reasons. First, they support the idea that in addition to being involved in processing reward prediction errors, DA neurons also modulate instrumental response output in several ways. Second, these results emphasize that modulation of DA neuron activity can affect both the instigation and maintenance of motivated behavior. Finally, they also provide substantial support for previous pharmacological and physiological research showing that DA transmission is involved in promoting the ability of organisms to exert effort and work toward motivationally significant goals (Salamone et al., 2016; Ko and Wanat, 2016; Hamid et al., 2016; Winstanley and Floresco, 2016; Boekhoudt et al., 2017; Wood et al., 2017).