Maintaining concentration on demanding cognitive tasks, such as vigilance (VG) and working memory (WM) tasks, is crucial for successful task completion. Previous research suggests that internal concentration maintenance fluctuates, potentially declining to suboptimal states, which can influence trial-by-trial performance in these tasks. However, the timescale of such alertness maintenance, as indicated by slow changes in pupil diameter, has not been thoroughly investigated. This study explored whether “pupil trends”—which selectively signal suboptimal tonic alertness maintenance at various timescales—negatively correlate with trial-by-trial performance in VG and WM tasks. Using the psychomotor vigilance task (VG) and the visual–spatial two-back task (WM), we found that human pupil trends lasting over 10 s were significantly higher in trials with longer reaction times, indicating poorer performance, compared with shorter reaction time trials, which indicated better performance. The attention network test fu...

It is widely believed that axons in the central nervous system of adult mammals do not regrow following injury. This failure is thought, at least in part, to underlie the limited recovery of function following injury to the brain or spinal cord. Some studies of fixed tissue have suggested that, counter to dogma, norepinephrine (NE) axons regrow following brain injury. Here, we have used in vivo two-photon microscopy in layer 1 of the primary somatosensory cortex in transgenic mice harboring a fluorophore selectively expressed in NE neurons. This protocol allowed us to explore the dynamic nature of NE axons following injury with the selective NE axon toxin N -(2-chloroethyl)- N -ethyl-2-bromobenzylamine (DSP4). Following DSP4, NE axons were massively depleted and then slowly and partially recovered their density over a period of weeks. This regrowth was dominated by new axons entering the imaged volume. There was almost no contribution from local sprouting from spared NE axons. Regrown axons did not appear ...

Founded in 1969, the Society for Neuroscience (SfN) now has nearly 35,000 members in more than 95 countries. Year-round programming includes the publishing of two highly regarded scientific journals, JNeurosci and eNeuro; professional development resources and career training through Neuronline¸ the Society’s home for learning and discussion; science advocacy and public policy engagement including annual Capitol Hill Day; and a variety of engaging public outreach efforts, led by the expanding and interactive collection of public-facing resources on BrainFacts.org.

Founded in 1969, the Society for Neuroscience (SfN) now has nearly 35,000 members in more than 95 countries. Year-round programming includes the publishing of two highly regarded scientific journals, JNeurosci and eNeuro; professional development resources and career training through Neuronline¸ the Society’s home for learning and discussion; science advocacy and public policy engagement including annual Capitol Hill Day; and a variety of engaging public outreach efforts, led by the expanding and interactive collection of public-facing resources on BrainFacts.org.

The importance of the dorsal hippocampus (DH) in mediating the memory-enhancing effects of the sex-steroid hormone 17β-estradiol (E2) is well established. However, estrogen receptors (ERs) are highly expressed in other brain regions that support memory formation, including the medial prefrontal cortex (mPFC). The mPFC and DH interact to mediate the formation of several types of memory, and behavioral tasks that recruit the mPFC are enhanced by systemic E2 administration, making this region a prime candidate for investigating circuit-level questions regarding the estrogenic regulation of memory. Further, infusion of E2 directly into the DH increases dendritic spine density in both the DH and mPFC, and this effect depends upon rapid activation of cell-signaling pathways in the DH, demonstrating a previously unexplored interaction between the DH and mPFC that led us to question the role of the mPFC in object memory consolidation and the necessity of DH-mPFC interactions in the memory-enhancing effects of E2. ...

Estrogens act through nuclear and membrane-initiated signaling. Estrogen receptor alpha (ERα) is critical for reproduction, but the relative contribution of its nuclear and membrane signaling to the central regulation of reproduction is unclear. To address this question, two complementary approaches were used: estetrol (E4) a natural estrogen acting as an agonist of nuclear ERs, but as an antagonist of their membrane fraction, and the C451A-ERα mouse lacking mERα. E4 dose- dependently blocks ovulation in female rats, but the central mechanism underlying this effect is unknown. To determine whether E4 acts centrally to control ovulation, its effect was tested on the positive feedback of estradiol (E2) on neural circuits underlying luteinizing hormone (LH) secretion. In ovariectomized females chronically exposed to a low dose of E2, estradiol benzoate (EB) alone or combined with progesterone (P) induced an increase in the number of kisspeptin (Kp) and gonadotropin-releasing hormone (GnRH) neurons coexpressin...

Aging and pathologic conditions cause intracellular aggregation of macromolecules and the dysfunction and degeneration of neurons, but the mechanisms are largely unknown. Prime examples are lysosomal storage disorders such as Niemann–Pick type C (NPC) disease, where defects in the endosomal–lysosomal protein NPC1 or NPC2 cause intracellular accumulation of unesterified cholesterol and other lipids leading to neurodegeneration and fatal neurovisceral symptoms. Here, we investigated the impact of NPC1 deficiency on rodent neurons using pharmacologic and genetic models of the disease. Improved ultrastructural detection of lipids and correlative light and electron microscopy identified lamellar inclusions as the subcellular site of cholesterol accumulation in neurons with impaired NPC1 activity. Immunogold labeling combined with transmission electron microscopy revealed the presence of CD63 on internal lamellae and of LAMP1 on the membrane surrounding the inclusions, indicating their origins from intraluminal ...

Brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) are known to contribute to both protective and pronociceptive processes. However, their contribution to neuropathic pain after spinal cord injury (SCI) needs further investigation. In a recent study utilizing TrkBF616A mice, it was shown that systemic pharmacogenetic inhibition of TrkB signaling with 1NM-PP1 (1NMP) immediately after SCI delayed the onset of pain hypersensitivity, implicating maladaptive TrkB signaling in pain after SCI. To examine potential neural mechanisms underlying the behavioral outcome, patch-clamp recording was performed in small-diameter dissociated thoracic (T) dorsal root ganglia (DRG) neurons to evaluate TrkB signaling in uninjured mice and after T10 contusion SCI. Bath-applied 7,8-dihydroxyflavone (7,8-DHF), a selective TrkB agonist, induced a robust inward current in neurons from uninjured mice, which was attenuated by 1NMP treatment. SCI also decreased 7,8-DHF-induced current while increasing th...

The social environment has long been recognized to play an important role in substance use, which is often modeled in rodents using operant conditioning. However, most operant chambers only accommodate one rodent at a time. We present PeerPub—a unique social operant chamber. PeerPub employs touch sensors to track the licking behavior on drinking spouts. When the number of licks meets a set reinforcement schedule, it dispenses a drop of solution with a fixed volume as a reward at the tip of the spout. A radio frequency identification (RFID) chip implanted in each rat’s skull identifies it throughout the experiment. The system is managed by a Raspberry Pi computer. We evaluated PeerPub using Sprague Dawley rats in daily 1 h sessions, where supersac (a glucose and saccharin solution) was provided under a fixed-ratio five schedule. We discovered that male rats consumed more supersac in dual rat conditions compared with single rat conditions. These findings illustrate PeerPub’s effectiveness in modeling the int...

Spencer P. Loewen, Dinara V. Baimoukhametova, and Jaideep S. Bains (see pages [8842–8852][1]) When an animal encounters a potentially dangerous situation, the brain initiates physiological and behavioral responses that can enhance survival. Activation of these responses also primes the