The ability to encode and retrieve contextual information is an inherent feature of episodic memory that starts to develop during childhood. The postrhinal cortex, an area of the parahippocampal region, has a crucial role in encoding object-space information and translating egocentric to allocentric representation of local space. The strong connectivity of POR with the adjacent entorhinal cortex, and consequently the hippocampus, suggests that the development of these connections could support the postnatal development of contextual memory. Here, we report that postrhinal cortex projections of the rat develop progressively from the first to the third postnatal week starting in the medial entorhinal cortex before spreading to the lateral entorhinal cortex. The increased spread and complexity of postrhinal axonal distributions is accompanied by an increased complexity of entorhinal dendritic trees and an increase of postrhinal – entorhinal synapses, which supports a gradual maturation in functional activity....

Metabolic state can alter olfactory sensitivity, but it is unknown if the activity of the olfactory bulb (OB) may fine tune metabolic homeostasis. Our objective was to use CRISPR gene editing in male and female mice to enhance the excitability of mitral/tufted projection neurons (M/TCs) of the OB to test for improved metabolic health. Ex vivo slice recordings of MCs in CRIPSR mice confirmed increased excitability due the targeted loss of Kv1.3 channels, which resulted in a less negative resting membrane potential, enhanced action potential firing, and insensitivity to the selective channel blocker margatoxin. CRISPR mice exhibited enhanced odor discrimination using a habituation/dishabituation paradigm. CRISPR mice were challenged for 25 weeks with a moderately high-fat diet, and compared with littermate controls, male mice were resistance to diet-induced obesity (DIO). Female mice did not exhibit DIO. CRISPR male mice gained less body weight, accumulated less white adipose tissue, cleared a glucose challe...

Schemata enhance memory formation for related novel information. This is true even when this information is neutral with respect to schema-driven expectations. This assimilation of novel information into schemata has been attributed to more effective organizational processing that leads to more referential connections with the activated associative schema network. Animal data suggest that systems consolidation of novel assimilated information is also accelerated. In the current study, we used both multivariate and univariate fMRI analyses to provide further support for these proposals and to elucidate the neural underpinning of these processes. 28 Participants (5 male) over-learned fictitious schemata for seven weeks and then encoded novel related and control facts in the scanner. These facts were retrieved both immediately and two weeks later, also in the scanner. Our results conceptually replicate previous findings with respect to enhanced vmPFC-hippocampus coupling during encoding of novel related infor...

While conflict between incompatible goals has well-known effects on actions, in many situations the same action may produce harmful or beneficial consequences during different periods in a non-conflicting manner –e.g., crossing the street during a red or green light. To avoid harm, subjects must be cautious to inhibit the action specifically when it is punished –as in passive avoidance, but act when it is beneficial –as in active avoidance or active approach. In mice of both sexes performing a signaled action to avoid harm or obtain reward, we found that addition of a new rule that punishes the action when it occurs unsignaled delays the timing of the signaled action in an apparent sign of increased caution . Caution depended on task signaling, contingency, and reinforcement type. Interestingly, caution became persistent when the signaled action was avoidance motivated by danger but was only transient when it was approach motivated by reward. Although caution is represented by the activity of neurons in th...

In human neurodegenerative diseases, neurons undergo axonal degeneration months to years before they die. Here, we developed a system modeling early degenerative events in Drosophila adult photoreceptor cells. Thanks to the stereotypy of their axonal projections, this system delivers quantitative data on sporadic and progressive axonal degeneration of photoreceptor cells. Using this method, we show that exposure of adult female flies to a constant light stimulation for several days overcomes the intrinsic resilience of R7 photoreceptors and leads to progressive axonal degeneration. This was not associated with apoptosis. We furthermore provide evidence that loss of synaptic integrity between R7 and a postsynaptic partner preceded axonal degeneration, thus recapitulating features of human neurodegenerative diseases. Finally, our experiments uncovered a role of postsynaptic partners of R7 to initiate degeneration, suggesting that postsynaptic cells signal back to the photoreceptor to maintain axonal structur...

Neonatal brain injury renders the developing brain vulnerable to oxidative stress, leading to cognitive deficit. However, oxidative stress-induced damage to hippocampal circuits and the mechanisms underlying long-term changes in memory and learning are poorly understood. We used high oxygen tension or hyperoxia (HO) in neonatal mice of both sexes to investigate the role of oxidative stress in hippocampal damage. Perinatal HO induces reactive oxygen species and cell death, together with reduced interneuron maturation, inhibitory postsynaptic currents, and dentate progenitor proliferation. Postinjury interneuron stimulation surprisingly improved inhibitory activity and memory tasks, indicating reversibility. With decreased hippocampal levels of Wnt signaling components and somatostatin, HO aberrantly activated glycogen synthase kinase 3 β activity. Pharmacological inhibition or ablation of interneuron glycogen synthase kinase 3 β during HO challenge restored progenitor cell proliferation, interneuron develop...

Aphasia is a prevalent cognitive syndrome caused by stroke. The rarity of premorbid imaging and heterogeneity of lesion obscures the links between the local effects of the lesion, global anatomic network organization, and aphasia symptoms. We applied a simulated attack approach in humans to examine the effects of 39 stroke lesions (16 females) on anatomic network topology by simulating their effects in a control sample of 36 healthy (15 females) brain networks. We focused on measures of global network organization thought to support overall brain function and resilience in the whole brain and within the left hemisphere. After removing lesion volume from the network topology measures and behavioral scores [the Western Aphasia Battery Aphasia Quotient (WAB-AQ), four behavioral factor scores obtained from a neuropsychological battery, and a factor sum], we compared the behavioral variance accounted for by simulated poststroke connectomes to that observed in the randomly permuted data. Global measures of anato...

In the article “Soluble α-Synuclein Is a Novel Modulator of Alzheimer's Disease Pathophysiology,” by Megan E. Larson, Mathew A. Sherman, Susan Greimel, Michael Kuskowski, Julie A. Schneider, David A. Bennett, and Sylvain E. Lesné, which appeared on pages [10253–10266][1] of the July 25, 2012

Grant P. Higerd-Rusli, Matthew Alsaloum, Sidharth Tyagi, Nivedita Sarveswaran, Mark Estacion, et al. (see pages [4794–4811][1]) Neuronal function, from synaptic integration to spike output, depends heavily on the type, expression level, and localization of ion channels in the plasma membrane.