It is controversial whether the effects of aging on various cognitive functions have the same common cause or several different causes. To investigate this issue, we scanned younger and older adults ...with functional magnetic resonance imaging (fMRI) while performing three different tasks: working memory, visual attention and episodic retrieval. There were three main results. First, in all three tasks, older adults showed weaker occipital activity and stronger prefrontal and parietal activity than younger adults. The occipital reduction is consistent with the view that sensory processing decline is a common cause in cognitive aging, and the prefrontal increase may reflect functional compensation. Secondly, older adults showed more bilateral patterns of prefrontal activity than younger adults during working memory and visual attention tasks. These findings are consistent with the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) model. Finally, compared to younger adults, older adults showed weaker hippocampal formation activity in all three tasks but stronger parahippocampal activity in the episodic retrieval task. The former finding suggests that age-related hippocampal deficits may have a global effect in cognition, and the latter is consistent with an age-related increase in familiarity-based recognition. Taken together, the results indicate that both common and specific factors play an important role in cognitive aging.
Primary pain and touch sensory neurons not only detect internal and external sensory stimuli, but also receive inputs from other neurons. However, the neuronal derived inputs for primary neurons have ...not been systematically identified. Using a monosynaptic rabies viruses-based transneuronal tracing method combined with sensory-specific Cre-drivers, we found that sensory neurons receive intraganglion, intraspinal, and supraspinal inputs, the latter of which are mainly derived from the rostroventral medulla (RVM). The viral-traced central neurons were largely inhibitory but also consisted of some glutamatergic neurons in the spinal cord and serotonergic neurons in the RVM. The majority of RVM-derived descending inputs were dual GABAergic and enkephalinergic (opioidergic). These inputs projected through the dorsolateral funiculus and primarily innervated layers I, II, and V of the dorsal horn, where pain-sensory afferents terminate. Silencing or activation of the dual GABA/enkephalinergic RVM neurons in adult animals substantially increased or decreased behavioral sensitivity, respectively, to heat and mechanical stimuli. These results are consistent with the fact that both GABA and enkephalin can exert presynaptic inhibition of the sensory afferents. Taken together, this work provides a systematic view of and a set of tools for examining peri- and extrasynaptic regulations of pain-afferent transmission.
Mitochondria are organized in the cell in the form of a dynamic, interconnected network. Mitochondrial dynamics, regulated by mitochondrial fission, fusion, and trafficking, ensure restructuring of ...this complex reticulum in response to nutrient availability, molecular signals, and cellular stress. Aberrant mitochondrial structures have long been observed in aging and age‐related diseases indicating that mitochondrial dynamics are compromised as cells age. However, the specific mechanisms by which aging affects mitochondrial dynamics and whether these changes are causally or casually associated with cellular and organismal aging is not clear. Here, we review recent studies that show specifically how mitochondrial fission, fusion, and trafficking are altered with age. We discuss factors that change with age to directly or indirectly influence mitochondrial dynamics while examining causal roles for altered mitochondrial dynamics in healthy aging and underlying functional outputs that might affect longevity. Lastly, we propose that altered mitochondrial dynamics might not just be a passive consequence of aging but might constitute an adaptive mechanism to mitigate age‐dependent cellular impairments and might be targeted to increase longevity and promote healthy aging.
Mitochondria form a dynamic, interconnected network that is shaped by fusion, fission and trafficking. This review discusses how aging affects mitochondrial dynamics and how such alterations in turn might help the organism to cope with age‐dependent cellular impairments.
A growing body of research suggests that comprehending verbal descriptions of actions relies on an internal simulation of the described action. To assess this motor resonance account of language ...comprehension, we first review recent developments in the literature on perception and action, with a view towards language processing. We then examine studies of language processing from an action simulation perspective. We conclude by discussing several criteria that might be helpful with regard to assessing the role of motor resonance during language comprehension.
The function of cortical GABAergic interneurons is largely determined by their integration into specific neural circuits, but the mechanisms controlling the wiring of these cells remain largely ...unknown. This is particularly true for a major population of basket cells that express the neuropeptide cholecystokinin (CCK). Here we found that the tyrosine kinase receptor ErbB4 was required for the normal integration into cortical circuits of basket cells expressing CCK and vesicular glutamate transporter 3 (VGlut3). The number of inhibitory synapses made by CCK
VGlut3
basket cells and the inhibitory drive they exerted on pyramidal cells were reduced in conditional mice lacking ErbB4. Developmental disruption of the connectivity of these cells diminished the power of theta oscillations during exploratory behavior, disrupted spatial coding by place cells, and caused selective alterations in spatial learning and memory in adult mice. These results suggest that normal integration of CCK
basket cells in cortical networks is key to support spatial coding in the hippocampus.
We examined the contribution of endogenous cholinergic signaling to the acquisition and extinction of fear- related memory by optogenetic regulation of cholinergic input to the basal lateral amygdala ...(BLA). Stimulation of cholinergic terminal fields within the BLA in awake-behaving mice during training in a cued fear-conditioning paradigm slowed the extinction of learned fear as assayed by multi-day retention of extinction learning. Inhibition of cholinergic activity during training reduced the acquisition of learned fear behaviors. Circuit mechanisms underlying the behavioral effects of cholinergic signaling in the BLA were assessed by in vivo and ex vivo electrophysiological recording. Photostimulation of endogenous cholinergic input (1) enhances firing of putative BLA principal neurons through activation of acetylcholine receptors (AChRs), (2) enhances glutamatergic synaptic transmission in the BLA, and (3) induces LTP of cortical-amygdala circuits. These studies support an essential role of cholinergic modulation of BLA circuits in the inscription and retention of fear memories.
•Photostimulation of ACh in BLA during cue-fear training makes memory more durable•Stimulating ACh input to BLA in vivo and ex vivo increases neuronal excitability•Stimulating ACh input to BLA can elicit LTP•All of the above effects are dependent on acetylcholine receptors (AChRs)
Jiang et al. demonstrate that manipulating BLA cholinergic input is important for emotional memory acquisition/retention. Stimulating ACh input increases principal neuron excitability and enhances glutamatergic synaptic plasticity in BLA. AChR antagonists block these effects.
The gastrointestinal tract is the only internal organ to have evolved with its own independent nervous system, known as the enteric nervous system (ENS). This Review provides an update on advances ...that have been made in our understanding of how neurons within the ENS coordinate sensory and motor functions. Understanding this function is critical for determining how deficits in neurogenic motor patterns arise. Knowledge of how distension or chemical stimulation of the bowel evokes sensory responses in the ENS and central nervous system have progressed, including critical elements that underlie the mechanotransduction of distension-evoked colonic peristalsis. Contrary to original thought, evidence suggests that mucosal serotonin is not required for peristalsis or colonic migrating motor complexes, although it can modulate their characteristics. Chemosensory stimuli applied to the lumen can release substances from enteroendocrine cells, which could subsequently modulate ENS activity. Advances have been made in optogenetic technologies, such that specific neurochemical classes of enteric neurons can be stimulated. A major focus of this Review will be the latest advances in our understanding of how intrinsic sensory neurons in the ENS detect and respond to sensory stimuli and how these mechanisms differ from extrinsic sensory nerve endings in the gut that underlie the gut-brain axis.
The fact that action observation, motor imagery and execution are associated with partially overlapping increases in parieto-frontal areas has been interpreted as evidence for reliance of these ...behaviors on a common system of motor representations. However, studies that include all three conditions within a single paradigm are rare, and consequently, there is a dearth of knowledge concerning the distinct mechanisms involved in these functions. Here we report key differences in neural representations subserving observation, imagery, and synchronous imitation of a repetitive bimanual finger-tapping task using fMRI under conditions in which visual stimulation is carefully controlled. Relative to rest, observation, imagery, and synchronous imitation are all associated with widespread increases in cortical activity. Importantly, when effects of visual stimulation are properly controlled, each of these conditions is found to have its own unique neural signature. Relative to observation or imagery, synchronous imitation shows increased bilateral activity along the central sulcus (extending into precentral and postcentral gyri), in the cerebellum, supplementary motor area (SMA), parietal operculum, and several motor-related subcortical areas. No areas show greater increases for imagery vs. synchronous imitation; however, relative to synchronous imitation, observation is associated with greater increases in caudal SMA activity than synchronous imitation. Compared to observation, imagery increases activation in pre-SMA and left inferior frontal cortex, while no areas show the inverse effect. Region-of-interest (ROI) analyses reveal that areas involved in bimanual open-loop movements respond most to synchronous imitation (primary sensorimotor, classic SMA, and cerebellum), and less vigorously to imagery and observation. The differential activity between conditions suggests an alternative hierarchical model in which these behaviors all rely on partially independent mechanisms.
► Compared neural representations for observation, imagery, and imitation with fMRI. ► Controlled visual stimulation reveals a hierarchical organization. ► Imitation > imagery or observation in sensorimotor cortex, SMA and cerebellum. ► Imagery > observation in pre-SMA, cerebellum, left IFg, insula, and cingulate Gyrus. ► Observation > imitation in caudalmost SMA.
The major function of the lower urinary tract is to store and periodically evacuate urine from the bladder. This requires coordination of the smooth muscles of the bladder and urethra, and of the ...striated muscles of the outflow region and pelvic floor by a complex neural control system. Lumbosacral afferent fibers (pelvic afferents), but also afferents in the hypogastric and pudendal nerves, are of major importance for the regulation of the mechanisms for continence and micturition. In the bladder, afferent nerves have been identified suburothelially as well as in the detrusor muscle. Suburothelially, they form a plexus that lies immediately beneath the epithelial lining. This plexus is particularly dense in the bladder neck and the trigone. The most important afferents for the micturition process are myelinated Aδ-fibers and unmyelinated C-fibers. Immunocytochemical and tracing studies have revealed that numerous peptides, including substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, enkephalins, and cholecystokinin are localized either alone, or in combination, in afferent pathways of the bladder and urethra. The receptors on these nerves include: vanilloid receptors, purinoceptors, tachykinin, and prostanoid receptors. Extracellular adenosine triphosphate (ATP) has been found to mediate excitation of small-diameter sensory neurons via P2X
3 receptors, and it has been proposed that in the bladder, distention causes release of ATP from the urothelium. ATP, in turn, can activate P2X
3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, it is most likely that a cascade of inhibitory and stimulatory transmitters/mediators, as well as ATP, are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling.
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