Activation of the Supplementary Motor Areas Enhances Spinal Reciprocal Inhibition in Healthy Individuals

The supplementary motor area (SMA) may modulate spinal reciprocal inhibition (RI) because the descending input from the SMA is coupled to interneurons in the spinal cord via the reticulospinal tract. Our study aimed to verify whether the anodal transcranial direct current stimulation (anodal-tDCS) of the SMA enhances RI. Two tDCS conditions were used: the anodal stimulation (anodal-tDCS) and sham stimulation (sham-tDCS) conditions. To measure RI, there were two conditions: one with the test stimulus (alone) and the other with the conditioning-test stimulation intervals (CTIs), including 2 ms and 20 ms. RI was calculated at multiple time points: before the tDCS intervention (Pre); at 5 (Int 5) and 10 min; and immediately after (Post 0); and at 5, 10 (Post 10), 15, and 20 min after the intervention. In anodal-tDCS, the amplitude values of H-reflex were significantly reduced for a CTI of 2 ms at Int 5 to Post 0, and a CTI of 20 ms at Int 5 to Pot 10 compared with Pre. Stimulation of the SMA with anodal-tDCS for 15 min activated inhibitory interneurons in RIs by descending input from the reticulospinal tract via cortico–reticulospinal projections. The results showed that 15 min of anodal-tDCS in the SMA enhanced and sustained RI in healthy individuals.

A mathematical model for storage and recovery of motor actions in the spinal cord

Motor outputs are generated by the spinal cord in response to de-scending inputs from the brain. While particular descending commands generate specific outputs, how descending inputs interact with spinal cord circuitry to generate these outputs remains unclear. Here, we suggest that during development particular motor programmes are stored in premotor spinal circuitry, and that these can subsequently be retrieved when the associated descending input is received. We propose that different motor patterns are not stored in the spinal cord as a library of separate programmes, but that the spinal cord orthogonalises and normalises the various inputs, identifies the similarities and differences between them, and stores only the differences: similarities between patterns are recognised and used as a common basis that subsequent input patterns are built upon. By removing redundancy this can greatly increase the storage capacity of a system composed of a finite number of processing units, thus overcoming the problems associated with the storage limits of conventional artificial networks (e.g. ‘catastrophic interference’). Where possible we relate the various stages of the processing to the known circuitry and synaptic properties of spinal cord locomotor networks, and suggest experimental approaches that could test unknown aspects.

Comparison of GABA, Somatostatin, and Corticotrophin-Releasing Hormone Expression in Axon Terminals That Target the Parabrachial Nucleus

Several forebrain areas have been shown to project to the parabrachial nucleus (PBN) and exert inhibitory and excitatory influences on taste processing. Some sources of descending input such as the central nucleus of the amygdala (CeA) might utilize somatostatin (Sst) and/or corticotrophin-releasing hormone (Crh) to influence taste processing in the PBN (Panguluri S, Saggu S, Lundy R. 2009. Comparison of somatostatin and corticotrophin-releasing hormone immunoreactivity in forebrain neurons projecting to taste-responsive and non-responsive regions of the parabrachial nucleus in rat. Brain Res 1298:57–69; Magableh A, Lundy R. 2014. Somatostatin and corticotrophin releasing hormone cell types are a major source of descending input from the forebrain to the parabrachial nucleus in mice. Chem Senses 39:673–682). Since the predominate effect of CeA stimulation on PBN taste-evoked responses is inhibition, this study used transgenic reporter lines (Sst/TdTomato and Crh/TdTomato) and electron microscopy to assess Sst/gamma aminobutyric acid (GABA) and Crh/GABA coexpression in axon terminals within the PBN. Robust expression of Sst and Crh axon terminals was observed in the PBN. The majority of Sst-positive axon terminals were positive for GABA expression, while the majority of Crh terminals were not. The results indicate that Sst-expressing neurons, but not Crh neurons, are a source of GABAergic input to the PBN. To assess whether the CeA is a source of GABAergic input to the PBN, the CeA of Sst-cre mice was injected with cre-dependent enhanced yellow fluorescent protein (EYFP) virus and PBN tissue processed for GABA and EYFP expression. Again, the majority of EYFP Sst-positive axon terminals in the PBN coexpressed GABA. Together, the present results suggest that CeA neurons marked by Sst expression represent a major extrinsic source of GABAergic input to the PBN and this could underlie the predominate inhibitory effect of CeA stimulation on taste-evoked responses in the PBN.

Modulation of motoneurone excitability during rhythmic motor outputs

In quadrupeds, special circuity located within the spinal cord, referred to as central pattern generators (CPGs), is capable of producing complex patterns of activity such as locomotion in the absence of descending input. During these motor outputs, the electrical properties of spinal motoneurones are modulated such that the motoneurone is more easily activated. Indirect evidence suggests that like quadrupeds, humans also have spinally located CPGs capable of producing locomotor outputs, albeit descending input is considered to be of greater importance. Whether motoneurone properties are reconfigured in a similar manner to those of quadrupeds is unclear. The purpose of this review is to summarize our current state of knowledge regarding the modulation of motoneurone excitability during CPG-mediated motor outputs using animal models. This will be followed by more recent work initially aimed at understanding changes in motoneurone excitability during CPG-mediated motor outputs in humans, which quickly expanded to also include supraspinal excitability.

Feedback optimizes neural coding and perception of natural stimuli

Growing evidence suggests that sensory neurons achieve optimal encoding by matching their tuning properties to the natural stimulus statistics. However, the underlying mechanisms remain unclear. Here we demonstrate that feedback pathways from higher brain areas mediate optimized encoding of naturalistic stimuli via temporal whitening in the weakly electric fish Apteronotus leptorhynchus. While one source of direct feedback uniformly enhances neural responses, a separate source of indirect feedback selectively attenuates responses to low frequencies, thus creating a high-pass neural tuning curve that opposes the decaying spectral power of natural stimuli. Additionally, we recorded from two populations of higher brain neurons responsible for the direct and indirect descending inputs. While one population displayed broadband tuning, the other displayed high-pass tuning and thus performed temporal whitening. Hence, our results demonstrate a novel function for descending input in optimizing neural responses to sensory input through temporal whitening that is likely to be conserved across systems and species.

Plasticity in the Regenerating Nervous System of the Lamprey, a “Simple” Vertebrate

Human spinal cord injury (SCI) results in long-lasting disabilities due to the failure of damaged neurons to regenerate. The barriers to axon regeneration in mammalian central nervous system (CNS) are so great, and the anatomy so complex that incremental changes in regeneration brought about by pharmacological or molecular manipulations can be difficult to demonstrate. By contrast, lampreys recover functionally after a complete spinal cord transection (TX), based on regeneration of severed axons, even though lampreys share the basic organization of the mammalian CNS, including many of the same molecular barriers to regeneration. And because the regeneration is incomplete, it can be studied by manipulations designed to either inhibit or enhance it. In the face of reduced descending input, recovery of swimming and other locomotor functions must be accompanied by compensatory remodeling throughout the CNS, as would be required for functional recovery in mammals. For such studies, lampreys have significant advantages. They have several large, identified reticulospinal (RS) neurons, whose regenerative abilities have been individually quantified. Other large neurons and axons are visible in the spinal cord and can be impaled with microelectrodes under direct microscopic vision. The central pattern generator for locomotion is exceptionally well-defined, and is subject to significant neuromodulation. Finally, the lamprey genome has been sequenced, so that molecular homologs of human genes can be identified and cloned. Because of these advantages, the lamprey spinal cord has been a fertile source of information about the biology of axon regeneration in the vertebrate CNS, and has the potential to serve as a test bed for the investigation of novel therapeutic approaches to SCI and other CNS injuries.

Improving outcome of sensorimotor functions after traumatic spinal cord injury

In the rehabilitation of a patient suffering a spinal cord injury (SCI), the exploitation of neuroplasticity is well established. It can be facilitated through the training of functional movements with technical assistance as needed and can improve outcome after an SCI. The success of such training in individuals with incomplete SCI critically depends on the presence of physiological proprioceptive input to the spinal cord leading to meaningful muscle activations during movement performances. Some actual preclinical approaches to restore function by compensating for the loss of descending input to spinal networks following complete/incomplete SCI are critically discussed in this report. Electrical and pharmacological stimulation of spinal neural networks is still in the experimental stage, and despite promising repair studies in animal models, translations to humans up to now have not been convincing. It is possible that a combination of techniques targeting the promotion of axonal regeneration is necessary to advance the restoration of function. In the future, refinement of animal models according to clinical conditions and requirements may contribute to greater translational success.

Descending projections from the nucleus accumbens shell excite activity of taste-responsive neurons in the nucleus of the solitary tract in the hamster

The nucleus of the solitary tract (NST) and the parabrachial nuclei (PbN) are the first and second relays in the rodent central taste pathway. A series of electrophysiological experiments revealed that spontaneous and taste-evoked activities of brain stem gustatory neurons are altered by descending input from multiple forebrain nuclei in the central taste pathway. The nucleus accumbens shell (NAcSh) is a key neural substrate of reward circuitry, but it has not been verified as a classical gustatory nucleus. A recent in vivo electrophysiological study demonstrated that the NAcSh modulates the spontaneous and gustatory activities of hamster pontine taste neurons. In the present study, we investigated whether activation of the NAcSh modulates gustatory responses of the NST neurons. Extracellular single-unit activity was recorded from medullary neurons in urethane-anesthetized hamsters. After taste response was confirmed by delivery of sucrose, NaCl, citric acid, and quinine hydrochloride to the anterior tongue, the NAcSh was stimulated bilaterally with concentric bipolar stimulating electrodes. Stimulation of the ipsilateral and contralateral NAcSh induced firings from 54 and 37 of 90 medullary taste neurons, respectively. Thirty cells were affected bilaterally. No inhibitory responses or antidromic invasion was observed after NAcSh activation. In the subset of taste cells tested, high-frequency electrical stimulation of the NAcSh during taste delivery enhanced taste-evoked neuronal firing. These results demonstrate that two-thirds of the medullary gustatory neurons are under excitatory descending influence from the NAcSh, which is a strong indication of communication between the gustatory pathway and the mesolimbic reward pathway.

What the bird’s brain tells the bird’s eye: the function of descending input to the avian retina

As Cajal discovered in the late 19th century, the bird retina receives a substantial input from the brain. Approximately 10,000 fibers originating in a small midbrain nucleus, the isthmo-optic nucleus (ION), terminate in each retina. The input to the ION is chiefly from the optic tectum which, in the bird, is the primary recipient of retinal input. These neural elements constitute a closed loop, the centrifugal visual system (CVS), beginning and ending in the retina, that delivers positive feedback to active ganglion cells. Several features of the system are puzzling. All fibers from the ION terminate in the ventral retina and an unusual axon-bearing amacrine cell, the target cell, is the postsynaptic partner of these fibers. While the rest of the CVS is orderly and retinotopic, target cell axons project seemingly at random, mostly to distant parts of the retina. We review here the most significant features of the anatomy and physiology of the CVS with a view to understanding its function. We suggest that many of the facts about this system, including some that are otherwise difficult to explain, can be accommodated within the hypothesis that the images of shadows cast on the ground or on objects in the environment, initiate a rapid and parallel search of the sky for a possible aerial predator. If a predator is located, shadow and predator would be temporarily linked together and tracked by the CVS.