Changes in the Motor Asymmetry and Structure of Mauthner Neurons of the Goldfish Resulting from Unilateral Visual Deprivation

We studied the effects of unilateral enucleation of the eye on the motor asymmetry of goldfish fries and morphometric characteristics of their Mauthner neurons, MNs (data of 3D reconstruction using serial slices). Enucleation of the right or left eye in ambidextral fishes resulted in stable preference of turnings during swimming toward the side of visual deafferentation and in a shift of the initial motor asymmetry coefficient (MAC) by 25%, on average. Ipsilateral enucleation of the eye in dextral and sinistral fishes intensified the initial motor asymmetry by 20%. Contralateral enucleation of the eye in dextral and sinistral fishes induced inversion of the motor asymmetry with a decrease in the MAC by 50%, on average. All operated fishes stably (within 3 months or more) preferred to turn toward the side of the enucleated eye. Morphological measurements showed that the size of the ventral dendrite of the MN contralateral with respect to the side of enucleation noticeably decreased. At the same time, this neuron (according to a shift in the motor asymmetry of the fish) became the functionally dominant unit. These data agree with the earlier supposition on a reciprocal relation between the level of functional activity of the MN and the size of its ventral dendrite. Selective changes in the dimension of the ventral dendrite of the MN receiving visual inputs probably resulted from the action of some endogenous trophic factor. The effect of this factor was enhanced after enucleation of the eye and the corresponding dysfunction of the contralateral visual input. A specific local change in the balance of neurotransmitter influences upon the MN ventral dendrite can play the role of such a factor. From the neurophysiological aspect, a decrease in the size of the ventral MN dendrite is a primary link in the chain of events resulting in modification of behavior; it leads to intensification of the integral functional activity of the MN and a shift of the motor asymmetry of the fish compensating, in such a way, the effect of unilateral visual deprivation.     

Morphological parameters of mauthner neurons of goldfishes with modified asymmetry of motor behavior

We examined the morphological peculiarities of Mauthner neurons, MNs, in goldfishes with a phenotypically different or an experimentally modified preference to perform rightward vs leftward turnings in the course of motor behavior; this preference was characterized by values of the motor asymmetry coefficient (MAC). 3D reconstruction of MNs was performed based on several histological sections; volumes of the soma, lateral and ventral dendrites (LD and VD, respectively), initial segment of the axon, as well as full volumes of the right and left neurons, were calculated. Differences between the above parameters were expressed as structural asymmetry coefficients (SACs). It was shown that clear orientation asymmetry of motor behavior of the fish is accompanied by differences in the dimensions of MNs and their compartments; MNs localized contralaterally with respect to the preferred turning side were considerably bigger than ipsilateral neurons. Experimental influences inducing inversion of the motor asymmetry of fishes inverted structural asymmetry of their MNs. In fishes with no phenotypical preference of the turning side and in individuals whose motor asymmetry was smoothed due to experimental influences (rotational stimulations), structural asymmetry of the MNs was also smoothed. Changes of the structural proportions developed, as a rule, due to decreases in the dimensions of one or both MNs and their compartments. The MAC value was in direct correlation with the value of SAC of the MNs and with values of this coefficient for the soma and the sum soma + LD. At the same time, reciprocal relations were found for the MAC and structural asymmetry of the VD; the decrease in the volume of VD was related to an increase in the preference of the contralateral turning side by the fish, and vice versa. In general, the results of our study demonstrate that both morphological and functional peculiarities of MNs correlate to a significant extent with such a form of motor behavior of fishes as realization of spontaneous turnings. Neirofiziologiya/Neurophysiology, Vol. 38, No. 1, pp. 18–31, January–February, 2006.     

离体运动神经元对腹外侧索刺激的突触反应特征

应用新片大鼠脊髓薄片运动神经元细胞内记录技术,对电刺激腹外侧索诱发的突触反应进行了电生理特性分析。结果在２８个测试的ＭＮ中,２２人有兴奋性突触后电位反应,其中２个跟随在抑制性突触反应这后,６个还对单或串刺激产生慢ＥＰＳＰ反应;ＶＬＦ－ＥＰＳＰ的潜伏期频数分布呈峰坡性偏态;同－ＭＮ的ＶＬＦ－ＥＰＳＰ与腹根ＥＰＳＰ间有典型的空间总和。     

Early postnatal maturation in vestibulospinal pathways involved in neck and forelimb motor control

To assess the organization and functional development of vestibulospinal inputs to cervical motoneurons (MNs), we have used electrophysiology (ventral root and electromyographic [EMG] recording), calcium imaging, trans‐synaptic rabies virus (RV) and conventional retrograde tracing and immunohistochemistry in the neonatal mouse. By stimulating the VIIIth nerve electrically while recording synaptically mediated calcium responses in MNs, we characterized the inputs from the three vestibulospinal tracts, the separate ipsilateral and contralateral medial vestibulospinal tracts (iMVST/cMVST) and the lateral vestibulospinal tract (LVST), to MNs in the medial and lateral motor columns (MMC and LMC) of cervical segments. We found that ipsilateral inputs from the iMVST and LVST were differentially distributed to the MMC and LMC in the different segments, and that all contralateral inputs to MMC and LMC MNs in each segment derive from the cMVST. Using trans‐synaptic RV retrograde tracing as well as pharmacological manipulation of VIIIth nerve‐elicited synaptic responses, we found that a substantial proportion of inputs to both neck and forelimb extensor MNs was mediated monosynaptically, but that polysynaptic inputs were also significant. By recording EMG responses evoked by natural stimulation of the vestibular apparatus, we found that vestibular‐mediated motor output to the neck and forelimb musculature became more robust during the first 10 postnatal days, concurrently with a decrease in the latency of MN discharge evoked by VIIIth nerve electrical stimulation. Together, these results provide insight into the complexity of vestibulospinal connectivity in the cervical spinal cord and a cogent demonstration of the functional maturation that vestibulospinal connections undergo postnatally. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1061–1077, 2016     

Effects of optokinetic stimulation on motor asymmetry in the goldfish

In goldfish fries, we examined the effect of the optomotor reaction (drive to swim toward moving images of vertical dark bars) on the behavioral motor asymmetry. Contralateral optokinetic stimulation of fishes (rotation of the bars against the direction preferred by fishes in their turnings) gradually smoothed and, later on, inverted the motor asymmetry, while the asymmetry underwent no modifications in the case of ipsilateral optokinetic stimulation (rotation of the bars in the direction similar to that preferred for turnings). Contralateral optokinetic stimulation also induced long-lasting inversion of the motor asymmetry of immobilized fishes deprived of the possibility to follow the movement of bar images. Ipsilateral optokinetic stimulation of fishes with the enucleation of the ipsilateral eye enhanced their motor asymmetry, while contralateral stimulation either did not modify the motor asymmetry of such individuals or inverted this feature. These data agree with the concept that, in fishes, one eye dominates and more actively provides tracking of the movement of bars, while another eye is a subdominant one. In general, we first found that the use of specific visual stimulation allows one to modify for a long time the behavioral motor asymmetry of the fishes, which, as is known, correlates with the morphofunctional asymmetry of Mauthner neurons (MNs). Visual information that activates MNs influences mostly the ventral dendrites of these neurons; thus, our findings allow us to believe that stimulations, which initiate the optomotor reaction, can serve as an adequate physiological model of natural visual stimulation of MNs (with projection of the respective influences on the ventral dendrites of the above cells). The use of such an experimental paradigm opens up new possibilities for studies of the role of these dendrites in the functions of MNs and of the plasticity of morphofunctional organization of these cells. Neirofiziologiya/Neurophysiology, Vol. 39, No. 2, pp. 133–145, March–April, 2007.     

刺激鲫鱼小脑腹外侧区诱发的Mauthner细胞兴奋性突触后电位

实验采用微电极胞内记录技术探查鲫鱼Mauthner细胞(M-细胞)对小脑刺激的电反应特征。电刺激鲫鱼小脑腹外侧部,可在双侧M-细胞胞体、腹侧树突和外侧树突近端记录到一种复合性兴奋性突触后电位(小脑诱发性EPSP)。小脑诱发性EPSP潜伏期较短(0.63±0.09 ms),持续时间较长(5.49±1.13 ms),幅度分级和刺激频率依从等特征。以较高强度刺激小脑常引起M-细胞顺向激活。多点胞内连续穿刺实验显示小脑诱发性EPSP起源于腹侧树突远端。实验结果提示,小脑-M-细胞通路可能包含一组长短不等的神经元链,它们根据链的短或长,由近及远依次投射在腹侧树突远端。     

Increased probability of repetitive spinal motoneuron activation by transcranial magnetic stimulation after muscle fatigue in healthy subjects

Triple stimulation technique (TST) has previously shown that transcranial magnetic stimulation (TMS) fails to activate a proportion of spinal motoneurons (MNs) during motor fatigue. The depression in size of the TST response, but no attenuation of the conventional motor-evoked potential, suggested increased probability of repetitive spinal MN activation during exercise, even if some MNs failed to discharge by the brain stimulus. Here we used a modified TST [quadruple stimulation (QuadS) and quintuple stimulation (QuintS)] to examine the influence of fatiguing exercise on second and third MN discharges after a single TMS in healthy subjects. This method allows an estimation of the percentage of double and triple discharging MNs. Following a sustained contraction of the abductor digiti minimi muscle at 50% maximal force maintained to exhaustion, the size of QuadS and QuintS responses increased markedly, reflecting that a greater proportion of spinal MNs was activated two or three times by the transcranial stimulus. The size of QuadS responses did not return to precontraction levels during 10-min observation time, indicating long-lasting increase in excitatory input to spinal MNs. In addition, the postexercise behavior of QuadS responses was related to the duration of the contraction, pointing to a correlation between repeated activation of MNs and the subject's ability to maintain force. In conclusion, the study confirmed that an increased fraction of spinal MNs fire more than once in response to TMS when the muscle is fatigued. Repetitive MN firing may provide an adaptive mechanism to maintain motor unit activation and task performance during sustained voluntary activity.     

Organized variability in the neuromuscular system: a survey of task-related adaptations.

This survey concerns the physiology of the neuromuscular system, as studied at the level of the single mammalian limb muscle and its motoneurones (MNs). Particular attention is devoted to the ways in which the properties and the organization of spinal MNs are adapted for the control of muscle (unit) force. These questions are discussed in relation to: a) The general and basic task of the system: providing a smooth and finely gradeable force by the mechanisms of rate- and recruitment-modulation of MN activity. b) Gradation problems in relation to specific peripheral requirements in connection with: (i) tasks of different duty-time (i.e. problems related to fatigue and endurance); (ii) tasks of different speed; (iii) task using different muscle lengths; (iv) tasks requiring different adjustment-gains. c) The adaptational properties of the neuromuscular system as it is subjected to long-term changes in its motor tasks. These matters are largely discussed in relation to experiments for studying the responses of the neuromuscular system to different patterns of chronic electrical stimulation. d) The manner in which the neuromuscular system, at the level of a single unidirectional muscle, is used for different motor programs. Evidence is summarized which shows the presence of task-related variations in MN recruitment patterns, and it is pointed out that such variations may be related to the intraspinal topography of the respective MNs. It is suggested that these task-related variations in MN recruitment behaviour might largely reflect topographic (and other) differences in the organization of spinal interneuronal systems responsible for the execution of different motor programs.     

Effects of Near-Threshold Stimulation of the Vestibular Apparatus on Postural Responses Evoked by Displacements of the Visualized Surrounding

In healthy subjects in the relaxed upward stance and perceiving a virtual visual environment (VVE), we recorded postural reactions to isolated visual and vestibular stimulations or their combinations. Lateral displacements of the visualized virtual scene were used as visual stimuli. The vestibular apparatus was stimulated by application of near-threshold galvanic current pulses to the proc. mastoidei of the temporal bones. Isolated VVE shifts evoked mild, nonetheless clear, body tilts readily distinguished in separate trials; at the same time, postural effects of isolated vestibular stimulation could be detected only after averaging of several trials synchronized with respect to the beginning of stimulation. Under conditions of simultaneous combined presentation of visual and vestibular stimuli, the direction of the resulting postural responses always corresponded to the direction of responses induced by VVE shifts. The contribution of an afferent volley from the vestibular organ depended on the coincidence/mismatch of the direction of motor response evoked by such a volley with the direction of response to visual stimulation. When both types of stimulations evoked unidirectional body tilts, postural responses were facilitated, and the resulting effect was greater than that of simple summation of the reactions to isolated actions of the above stimuli. In the case where isolated galvanic stimulation evoked a response opposite with respect to that induced by visual stimulation, the combined action of these stimuli of different modalities evoked postural responses identical in their magnitude, direction, and shape to those evoked by isolated visual stimulation. The above findings allow us to conclude that the effects of visual afferent input on the vertical posture under conditions of our experiments clearly dominate. In general, these results confirm the statement that neuronal structures involved in integrative processing of different afferent volleys preferably select certain type of afferentation carrying more significant or more detailed information on displacements (including oscillations) of the body in space.     

A reflex behavior mediated by monosynaptic connections between hair afferents and motoneurons in the larval tobacco hornworm,Manduca sexta

In the tobacco hornworm caterpillar, tactile stimulation of sensory hairs located on the tip of a proleg (the planta) evokes ipsilateral or bilateral retraction of the prolegs in that segment. We have used electrophysiological and anatomical methods to investigate the excitatory neural pathways linking the planta hair afferents and the proleg retractor motoneurons (MNs). An important technical innovation was the development of an isolated proleg and desheathed ganglion preparation that permits rapid and reversible ionic manipulations and drug applications. Action potentials (spikes) in individual planta hair afferents produce time-locked excitatory postsynaptic potentials (EPSPs) in ipsilateral proleg MNs which appear to be chemically-mediated and monosynaptic: the EPSPs have a short and constant latency, they follow afferent spikes without failure, they are reversibly abolished in elevated Mg++ saline, and they persist in saline with elevated Mg++ and Ca++ levels. Planta hair afferents also excite ipsilateral MNs by polysynaptic pathways, and their excitation of contralateral proleg MNs is exclusively polysynaptic. Cobalt-staining of the proleg MNs and planta hair afferents shows that the afferents terminate in ventral neuropil, and the proleg MNs have an unusual ventral projection into this region. The ventral projection is on the ipsilateral side, which is consistent with the electrophysiological finding that time-locked EPSPs are found only from ipsilateral hairs. Two factors that contribute to the strong monosynaptic excitation of proleg MNs by ipsilateral planta hairs are the convergence of many hair afferents onto each MN, and the facilitation shown at each afferent-MN synapse. At least 6 afferents converge on each MN, and at short interspike intervals the afferent-evoked EPSPs are enhanced by as much as 400% by homosynaptic facilitation. The EPSP is abolished reversibly by the cholinergic antagonists curare and atropine, suggesting that the neurotransmitter at the synapse is acetylcholine (ACh). This is of particular interest because the ACh receptors of tobacco-feeding Manduca larvae are reported to be less nicotine-sensitive than those of other insects.     

Ultrastructure of the Mauthner neurons in goldfish fry after their adaptation to vestibular stimulation

The ultrastructure of the Mauthner cells (M-cells) of goldfish fries was investigated under four different functional states: a) intact (native fishes), b) fatigue (intact fishes subjected to a prolonged vestibular stimulation), c) adapted (intact fishes after a prolonged training session of the daily short vestibular stimuli), d) excited (adapted fishes subjected to a prolonged vestibular stimulation). It has been first found that the fatigue of the M-cells may result in destructive changes of their cytoskeleton. Besides, in the afferent synapses of both adapted and excited M-cells numerous dense-cored vesicles were revealed near the active zones. The data show the neuronal cytoskeleton to be the central target susceptible to damage upon stimulation. The training leads presumably to stabilization of the cytoskeleton ultrastructure. The dense-cored vesicles were suggested to play an active role in the process.     

Medullary neurons in the core white matter of the olfactory bulb: a new cell type

The structure of a new cell type, termed the medullary neuron (MN) because of its intimate association with the rostral migratory stream (RMS) in the bulbar core, is described in the adult rat olfactory bulb. The MN is a triangular or polygonal interneuron whose soma lies between the cellular clusters of the RMS or, less frequently, among the neuron progenitors therein. MNs are easily distinguished from adjacent cells by their large size and differentiated structure. Two MN subtypes have been categorized by the Golgi technique: spiny pyramidal neurons and aspiny neurons. Both MN subtypes bear a large dendritic field impinged upon by axons in the core bulbar white matter. A set of collaterals from the adjacent axons appears to terminate on the MN dendrites. The MN axon passes in close apposition to adjacent neuron progenitors in the RMS. MNs are immunoreactive with antisera raised against gamma-aminobutyric acid and glutamate decarboxylase 65/67. Electron-microscopic observations confirm that MNs correspond to fully differentiated, mature neurons. MNs seem to be highly conserved among macrosmatic species as they occur in Nissl-stained brain sections from mouse, guinea pig, and hedgehog. Although the functional role of MNs remains to be determined, we suggest that MNs represent a cellular interface between endogenous olfactory activity and the differentiation of new neurons generated during adulthood.     

A CRMP4‐dependent retrograde axon‐to‐soma death signal in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal non‐cell‐autonomous neurodegenerative disease characterized by the loss of motor neurons (MNs). Mutations in CRMP4 are associated with ALS in patients, and elevated levels of CRMP4 are suggested to affect MN health in the SOD1^G93A‐ALS mouse model. However, the mechanism by which CRMP4 mediates toxicity in ALS MNs is poorly understood. Here, by using tissue from human patients with sporadic ALS, MNs derived from C9orf72‐mutant patients, and the SOD1^G93A‐ALS mouse model, we demonstrate that subcellular changes in CRMP4 levels promote MN loss in ALS. First, we show that while expression of CRMP4 protein is increased in cell bodies of ALS‐affected MN, CRMP4 levels are decreased in the distal axons. Cellular mislocalization of CRMP4 is caused by increased interaction with the retrograde motor protein, dynein, which mediates CRMP4 transport from distal axons to the soma and thereby promotes MN loss. Blocking the CRMP4‐dynein interaction reduces MN loss in human‐derived MNs (C9orf72) and in ALS model mice. Thus, we demonstrate a novel CRMP4‐dependent retrograde death signal that underlies MN loss in ALS.     

Early axonal contacts during development of an identified dendrite in the brain of the zebrafish

We have identified the initial synaptic contacts made onto the Mauthner (M) cell, an identified neuron that arises during early development of the zebrafish hindbrain. The contacts are made by a small bundle of pioneering trigeminal sensory axons onto the M cell soma before it forms dendrites. The sensory bundle is then partially enveloped by the M cell. The lateral dendrite appears at about the site of the contact, and eventually the trigeminal inputs are shifted to its trunk. As the dendrite elongates, other sensory contacts are made on its distal regions, sequentially from the acoustico-vestibular nerve and the lateral line nerves. To learn whether the earliest inputs induce the initial outgrowth of the M cell dendrite, we ablated the trigeminal neurons by laser irradiation before they contacted the M cell. Morphogenesis of the M cell, including its dendrite, appeared normal.     

The convergent properties of the neocortical vestibular area in the cat]

In acute experiments on cats under nembutal-chloralose anaesthesia the evoked potentials and cellular reactions were studied of suprasylvian vestibular and auditory projection zones to stimulation of vestibular, acoustic and visual nerves and frontal paw. It has been shown that the suprasylvian vestibular zone represents the region of convergence of vestibular, auditory, somatic and visual afferentation. Properties of summary and cellular reactions of the vestibular zone and also the character of interaction of the evoked potentials of homo- and heteromodal origin testify to the absence of significant dominance of vestibular input to this area of the cerebral cortex in cats. Limitation of spreading of labyrinth activity in the cerebral cortex and the absence of dominance of homomodal input in the projection zone should, probably, be considered as typical property of the vestibular system presentation in the cortex, determining the disability of monomodal specific reaction in the sensory-perceptive sphere.     

Intersegmental interneurons serving larval and pupal mechanosensory reflexes in the moth Manduca sexta

1. Intersegmental interneurons (INs) that participate in the larval bending reflex and the pupal gin trap closure reflex were identified in the isolated ventral nerve cord of Manduca sexta. INs 305, 504, and 703 show qualitatively different responses in the pupa than in the larva to electrical stimulation of sensory neurons that are retained during the larval-pupal transition to serve both reflexes. Action potentials produced by current injected into the 3 interneurons excite motor neurons that are directly involved in the larval and pupal reflexes. The excitation of the motor neurons is not associated with EPSPs at a fixed latency following action potentials in the interneurons, and thus there do not seem to be direct synaptic connections between the interneurons and the motor neurons. 2. IN 305 (Fig. 2) has a lateral soma, processes in most of the dorsal neuropil ipsilateral to the soma, and a crossing neurite that gives rise to a single contralateral descending axon. IN 305 is excited by stimulation of the sensory nerve ipsilateral to its soma in the larva and the pupa. Stimulation of the sensory nerve contralateral to its soma produces an inhibitory response in the larva, but a mixed excitatory/inhibitory response to the identical stimulus in the pupa. 3. IN 504 (Fig. 3) has a lateral soma, processes throughout most of the neuropil ipsilateral to the soma, and a crossing neurite that bifurcates to give rise to a process extending to the caudal limit of the neuropil and an ascending axon. IN 504 is excited by stimulation of the sensory nerve ipsilateral to its soma in both larvae and pupae, while the response to stimulation of the sensory nerve contralateral to its soma is inhibitory in the larva but mixed (excitatory/inhibitory) in the pupa. 4. IN 703 has a large antero-lateral soma, a neurite that extends across to the contralateral side giving rise to processes located primarily dorsally in both ipsilateral and contralateral neuropils, and two axons that ascend and descend in the connectives contralateral to the soma (Fig. 4). IN 703 responds to stimulation of the sensory nerves on either side of the ganglion, but the form of the response changes during the larval-pupal transition. In the larva, the response consists of very phasic (0-2 spikes) excitation, but in the pupa there is a prolonged excitation that greatly outlasts the stimulus (Fig. 6).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of optokinetic stimulation on visual–manual tracking under the conditions of support-proprioceptive deprivation

The effects of additional dynamic visual stimuli (retinal optokinetic stimulation (ROKS)) on the visual–manual tracking (VMT) indicators in the absence of support afferentation and with a reduced level of proprioceptive afferentation were determined using a model of horizontal “dry” immersion. The accuracy of the VMT of jerky and smooth (linear, pendular, and circular) movements represented by visual dot stimuli was evaluated in all 18 participants aged 19–31 before, during and after their exposure to a five- to seven-day immersion bath. The eye movements were recorded by electrooculography, while the hand movements were recorded by a joystick with a biological visual feedback (the current angle of the joystick handle was imaged on the screen). Computerized visual stimulation tests were presented, through virtual reality glasses, to subjects in the absence and against the background ROKS. We analyzed the temporal and the amplitude- and velocity-related visual and manual tracking (VT and MT) characteristics, including the efficiency (e) and gain (g) coefficients as the ratios between the amplitudes and velocities of eye/hand movements and the amplitude of stimulus movements. The efficiency and gain coefficients of both VT and MT without ROKS were significantly decreased against the baseline during the entire period including three days of immersion and 3 post-immersion days. The most pronounced worsening was observed in the VT parameters. Whereas the VT and MT parameters remained unchanged against the threshold ROKS before the immersion, they were improved during and after the immersion (the improvement was significant on the fifth to seventh day of immersion and on the thirdthird post-immersion day, compared to the test indicators on the clean screen). The most pronounced impact of ROKS was observed in the VT parameters. The vestibular function (VF) was evaluated by videooculography before and after immersion. We analyzed the static torsional otolith-cervicalocular reflex (OCOR), dynamic vestibular-cervical-ocular reactions (VCOR), vestibular reactivity (VR), and spontaneous eye movements (SpEM). A significant decrease in OCOR (gOCOR was 0.1, compared to the background gOCOR value of 0.25) was detected alongside a simultaneous significant increase in the VCOR/VR parameters in 28% of subjects on day R + 1 after immersion. Correlational has been found between the parameters of VT and MT, as well as between those of VF and VT, but no correlation has been found between the VF and MT characteristics. The results have shown that the removal of support afferentation and the minimization of proprioceptive afferentation more affected the accuracy of VT rather than that of MT. The correlational links between the studied parameters against the background of ROKS were not only preserved, but also intensified. The obtained results confirm the development of sensory deprivation (and afferent deficit) under the exposure to an immersion bath and indicate the approach to correcting the sensory deprivation through additional ROKS.     

Autophagy, and BiP level decrease are early key events in retrograde degeneration of motoneurons

Disconnection of the axon from the soma of spinal motoneurons (MNs) leads either to a retrograde degenerative process or to a regenerative reaction, depending on the severity and the proximity to the soma of the axonal lesion. The endoplasmic reticulum (ER) is a continuous membranous network that extends from the nucleus to the entire cytoplasm of the neuronal soma, axon and dendrites. We investigated whether axonal injury is sensed by the ER and triggers the activation of protective mechanisms, such as the unfolded protein response (UPR) and autophagy. We found early (at 3 days) accumulation of beclin1, LC3II and Lamp-1, hallmarks of autophagy, in both degenerating MNs after spinal root avulsion and in non-degenerating MNs after distal nerve section, although Lamp-1 disappeared by 5 days only in the former. In contrast, only degenerating MNs presented early activation of IRE1α, revealed by an increase of the spliced isoform of Xbp1 and accumulation of ATF4 in their nucleus, two branches of the UPR, and late BiP downregulation in association with cytoskeletal and organelle disorganization. We conclude that BiP decrease is a signature of the degenerating process, as its overexpression led to an increase in MN survival after root avulsion. Besides, Bcl2 is strongly implicated in the survival pathway activated by BiP overexpression.