Ismael Jiménez

Functional and morphological effects of repeated sodium arsenite exposure on rat peripheral sensory nerves

Exposure to inorganic arsenic (iAs) is known to result in peripheral neuropathy. To better understand the functional and morphological consequences of iAs exposure, we examined the electrophysiological and histological characteristics of the sensory sural nerves in adult Male Wistar rats following 30 days of sodium arsenite administration by gavage (10 mg/kg body weight/day). Arsenic (As) levels in the peripheral nerves of exposed animals were about 150 times greater than those in controls. Lipid peroxidation was also increased in iAs-exposed animals. Compound action potentials (CAPs) evoked in iAs-exposed nerves were characterized by a slower conduction velocity ( approximately 26%). iAs-exposed nerves also showed a trend towards a decreased CAP area ( approximately 35%). These electrophysiological changes were consistent with histological alterations such as a approximately 56% decrease in myelin thickness. In addition, the perimeter and transverse area of axons were reduced to 29% and 45% of control, respectively. Our results suggest that accumulation of As produced by iAs exposure induces oxidative damage, severe demyelination, and other morphological alterations in axons of peripheral nerves. These changes may, in turn, induce changes in the generation and propagation of action potentials in peripheral nerves, leading to decreased transmission of information from peripheral sensory organs to the central nervous system.

Changes in correlation between spontaneous activity of dorsal horn neurones lead to differential recruitment of inhibitory pathways in the cat spinal cord

•  We have examined the functional organization of the neuronal ensembles involved in the generation of spontaneous cord dorsum potentials in the lumbo‐sacral spinal cord of the anaesthetized cat. •  These potentials appear synchronously along several spinal segments and are generated by a longitudinally distributed network of bilaterally interconnected sets of dorsal horn neurones. •  Low levels of synchronization of spontaneous neuronal activity within this network appear associated with activation of spinal pathways mediating glycinergic non‐reciprocal postsynaptic inhibition of motoneurones. •  During states of spontaneous increased synchronization, or after the acute section of cutaneous nerves, there is a preferential activation of the GABAergic pathways producing primary afferent depolarization and presynaptic inhibition of muscle and cutaneous afferents. •  It is suggested that modulation of the temporal synchronization of spontaneous activity of dorsal horn neurones might provide means for selection of alternatively operating inhibitory spinal pathways during different sensory and motor behaviours.

Multichannel Detrended Fluctuation Analysis Reveals Synchronized Patterns of Spontaneous Spinal Activity in Anesthetized Cats

The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA- mean = 1.040.09) or simultaneously from several lumbar segments (mDFA- mean = 1.010.06), where  = 0.5 indicates randomness while 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA- = 0.992 as compared to initial conditions mDFA- = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA- = 0.924). In contrast to the classical methods, such as correlation and coherence quantification that define a relation between two sets of data, the mDFA method properly reveals the synchronization of multiple groups of neurons in several segments of the spinal cord. This method is envisaged as a useful tool to characterize the structure of higher order ensembles of cord dorsum spontaneous potentials after spinal cord or peripheral nerve lesions.

Differences in morphology and contractility of the bulbospongiosus and pubococcygeus muscles in nulliparous and multiparous rabbits

In women, birth trauma can result in altered anatomy of supporting structures of the pelvic floor and in the development of urinary incontinence. The goal of this study was to investigate the association between parturition and the morphology and function of perineal and pelvic muscles in the female rabbit. In ten nulliparous and ten multiparous same-age females, we investigated morphological, histological (n = 5 females/group), and contractile characteristics (n = 5 females/group) of the perineal bulbospongiosus (Bsm) and the pelvic pubococcygeus (Pcm) muscles. Bsm and Pcm muscles of multiparous females were significantly lighter, they had a smaller cross-sectional fiber area, and developed significantly lower twitch and tetanic tension force in response to electrical stimulation than muscles of nulliparous females. In female rabbits, multiparity is associated with potentially pathological changes in the morphological and functional characteristics of these perineal and pelvic muscles, possibly as a result of stretching during parturition.

Effects of spinal and peripheral nerve lesions on the intersegmental synchronization of the spontaneous activity of dorsal horn neurons in the cat lumbosacral spinal cord

In the anesthetized and paralyzed cat, spontaneous negative cord dorsum potentials (nCDPs) appeared synchronously in the L3 to S1 segments, both ipsi- and contralaterally. The acute section of both the intact sural and the superficial peroneal nerve increased the variability of the spontaneous nCDPs without affecting their intersegmental coupling. On the other hand, the synchronization between the spontaneous nCDPs recorded in segments L5-L6 was strongly reduced following an interposed lesion of the left (ipsilateral) dorsolateral spinal quadrant and it was almost completely abolished by an additional lesion of the contralateral dorsolateral quadrant at the same level. Our observations support the existence of a system of spontaneously active dorsal horn neurons that is bilaterally distributed along the lumbosacral segments and affects, in a synchronized and organized manner, impulse transmission along many reflex pathways, including those mediating presynaptic inhibition.

6-Hydroxydopamine lesion in thalamic reticular nucleus reduces anxiety behaviour in the rat.

We have studied the effect of the lesion of the dopaminergic innervation of the thalamic reticular nucleus (TRn) on anxiety and motor behaviour. The lesion of the dopamine innervation was produced by the injection of 6-hydroxydopamine into the dorsal part of the thalamic reticular nucleus. The lesion decreased the number of TH (+) cells of the pars compacta of substantia nigra by 33%, without modifying the number of TH (+) cells in ventral tegmental area. The lesion increased the time spent by the rats on the open arms of the elevated plus maze and decreased the duration of burying in the shock-probe test. Both results suggest reduced anxiety. The loss of the dopamine innervation to the TRn decreased the number of rearings but did not significantly affect total motor activity, gait or motor coordination, as evidenced by rotarod performance. These findings suggest that dopamine in the TRn plays a role in fear-related behaviour.

Conduction failure of action potentials in sensory sural nerves of undernourished rats

In order to determine possible functional and morphometrical alterations produced by perinatal undernourishment on peripheral nerves, sensory sural nerves from control and undernourished rats of 30 and 90 postnatal days of age were dissected and divided in two segments, one for recording the compound action potential (CAP) and the other for histological examination. Nerves from undernourished animals showed maximal CAP responses of smaller amplitude and area, larger trial-to-trial variability in area, and a significant reduction in axonal myelin sheath thickness than nerves from control animals. It is suggested that perinatal undernourishment produces changes in axonal myelin sheath structure, resulting in severe alterations in the generation and propagation of action potentials (block and/or intermittent conduction) in sensory afferent fibers in the rat.

Absence of linear correlation between fluctuations in area of simultaneous recorded monosynaptic responses and Hoffmann's reflexes in the rat

In this study we analyze the possible relationship between fluctuations in area of monosynaptic reflex responses (MSR) and Hoffmanns reflex (H reflexes) in the plantar closed loop pathway of the anesthetized rat. These reflexes were evoked by low-frequency stimuli applied to the sciatic nerve or lateral plantar nerve and then concurrently recorded on the distal tibial nerve or lateral plantar nerve, respectively as well as the lateral plantar muscles in the foot of the anesthetized rat. From trial to trial, H reflexes showed higher variability in area than MSR, whether the latter was recorded in the distal tibial nerve (n=8 experiments) or in the lateral plantar nerve (n=5 experiments). No linear correlation was found between changes in area of concurrently evoked MSR and H reflexes (r(MSR-H,n=8)=0.11+/-0.03 and r(MSR-H,n=5)=0.08+/-0.09, respectively). These findings suggest that trial-to-trial fluctuations in area of H reflexes may involve interaction of several sources of variation, among others to MSR variability (due to pre-, and post-synaptic factors influencing the excitability of spinal motoneurons) in combination with those related to peripheral mechanisms, such as trial to trial activation of a different number of muscle fibers, either by the probabilistic transmitter release from neuromuscular junctions, by activation of motor units of variable size or to fluctuations in excitability of muscle fibers.

Differential presynaptic control of the synaptic effectiveness of cutaneous afferents evidenced by effects produced by acute nerve section.

•  We investigated, in the anaesthetized cat, the effects of acute section of the saphenous and superficial peroneal nerves on the synaptic effectiveness of the sural nerve afferents. •  We found that acute section of these nerves produced a long‐lasting increase of the sural‐evoked field potentials. At the same time, sural afferents ending within Rexeds laminae III–IV showed a reduced tonic primary afferent depolarization, while sural afferents projecting deeper into the dorsal horn (Rexeds laminae V–VI) instead showed increased tonic primary afferent depolarization. •  It is suggested that a differential control of the synaptic effectiveness of the low‐threshold cutaneous afferents according to their sites of termination within the dorsal horn provides means for a selective processing of sensory information in response to tactile and nociceptive stimulation or during the execution of different motor tasks.