Normal Innervation Pattern Research Articles

The Enteric Nervous System in Intestinal Inflammation

Since about the 1950s nerves in the wall of the intestine have been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD). Human and animal studies examining the role of nerves in intestinal inflammation are the focus of this review. Consideration is given to two possible ways that nerves are involved in IBD. First, nerves may play a role in the development or maintenance of inflammation through local release of transmitters. Second, once initiated (by whatever means), the processes of inflammation may disrupt the normal pattern of innervation and the interactions of nerves and their target tissues. Many of the functional disturbances observed in IBD are likely due to an alteration in the enteric nervous system either structurally through disruptions of nerve-target relationships or by modifications of neurotransmitters or their receptors. Finally, it appears that the enteric nervous system may be a potential therapeutic target in IBD and that neuroactive drugs acting locally can represent useful agents in the management of this disease.

Heterogeneity of the human myocardial sympathetic innervation: In vivo demonstration by iodine 123-labeled meta-iodobenzylguanidine scintigraphy

The normal pattern of the myocardial sympathetic innervation was studied in 15 subjects using single photon emission computed tomography (SPECT) gamma scintigraphy with iodine 123-labeled meta-iodobenzylguanidine (I 123MIBG). Seven young subjects (mean age 29.4 ± 7.5 years SD) with supraventricular tachycardia and eight older patients (mean age 53.0 ± 5.1 years SD) with normal coronary arteries at cardiac catheterization and normal thallium-201 scintigrams were studied. MIBG uptake in the hearts of six patients with complete cardiac denervation after orthotopic cardiac transplantation was also studied. MIBG scintigrams were reconstructed into bull's-eye target plots and divided into eight equal sectors. Within each sector, four areas representing the apical, two midventricular, and basal regions were defined. There was a reduction in counts in the older group of subjects with normal coronary anatomy (1218.2 ± 198.4) as compared with younger subjects with supraventricular tachycardia (1124.4 ± 317.6), (F = 15.0, df = 1, p < 0.001). The difference was lost after adjustment for age ( p = 0.2) by means of analysis of covariance. There was a difference in counts within different sectors of the scan (F = 5.7, df = 7, p < 0.001), with lateral and anterior sectors having higher counts than septal and inferior sectors. There was no difference in the counts within areas of the scan (F = 0.04, df = 3, not significant [NS]) or different areas within the sectors (F = 1.1, df = 21, NS). A small diminution of counts (approximately 10%) in the 10 o'clock region of the bull's-eye target plot was observed in some scans. There was no uptake of MIBG above background levels in the hearts of patients who had undergone cardiac transplantation despite normal perfusion on thallium-201 scintigraphy. These data suggest that there is heterogeneity of the cardiac sympathetic innervation, with fewer catecholaminergic nerve terminals in the inferior and septal walls of the left ventricle. However, cardiac sympathetic nerve terminals do not differ in distribution in the apical to basal regions. Cardiac sympathetic innervation appears to diminish with age. After cardiac transplantation patients do not appear to have evidence of sympathetic nerve terminals within the myocardium. We conclude that there is a degree of heterogeneity of MIBG uptake in normal hearts and that the abnormalities observed in pathologic conditions should be interpreted with caution in light of these findings.

Expression of NGF in sympathetic neurons leads to excessive axon outgrowth from ganglia but decreased terminal innervation within tissues

The effects of nerve growth factor (NGF) on sympathetic axon growth were investigated by generating transgenic mice in which the β subunit of NGF was expressed in sympathetic neurons using the human dopamine β-hydroxylase (DBH) promoter. In DBH-NGF mice, the sympathetic trunk and nerves growing to peripheral tissues were enlarged and contained an increased number of sympathetic fibers. Although sympathetic axons reached peripheral tissues, terminal sympathetic innervation within tissues was decreased in DBH-NGF mice. This effect could be reversed in the pancreas by overexpression of NGF in pancreatic islets. The observations are consistent with a model in which NGF gradients are not required to guide sympathetic axons to their targets, but are required for the establishment of the normal density and pattern of sympathetic innervation within target tissues.

Pure Schwann cell suspension grafts promote regeneration of the lesioned septo-hippocampal cholinergic pathway

Regeneration of central nervous system (CNS) axons has been studied in the cholinergic septo-hippocampal system using various ‘bridges’ able to support fiber growth. In this study, a pure Schwann cell (Sc) suspension labeled with bisbenzimide (Hoechst 33342) was grafted in the lesioned septo-hippocampal pathway. At 2 weeks post-grafting, acetyl-cholinesterase (AChE)-positive fibers invaded the graft and grew in association with the Hoechst-labeled Sc, some of which expressed the low-affinity nerve growth factor receptor (NGF-R). At 2 months and 4 months post-grafting, the dorsal hippocampus was reinnervated with an apparently normal innervation pattern. Analysis of fiber growth in the hippocampus at four months post-grafting revealed a significant increase of reinnervation in the grafted animals (2 mm) compared to the non-grafted ones. No difference was observed in the number of cholinergic septal neurons expressing the NGF-R. These results demonstrate that a Sc suspension grafted into the lesioned septo-hippocampal system, integrates well into the host tissue, and supports axonal CNS outgrowth, implying that Sc by themselves provide an adequate environment for regeneration to occur.

Mechanical and morphological properties of chronically inactive cat tibialis anterior motor units.

1. The lumbar spinal cord was functionally isolated in ten cats by cord transection at the junctions of segments T12-T13 and L7-S1 and cutting bilaterally all dorsal roots between the two transections. Two 24 h EMG recording sessions were used to verify that muscles in the lower limb were virtually electrically silent. The cats were maintained in excellent health for 6 months. 2. Six months after spinal cord isolation, an acute experiment was performed to isolate a single motor unit from the tibialis anterior of each hindlimb using ventral root splitting techniques. Each motor unit was characterized physiologically as either fast fatigable (FF, n = 11), fast fatigue resistant (FR, n = 4), fast intermediate (FI, n = 2), or slow (S, n = 1), and repetitively stimulated to deplete the motor unit of its glycogen. 3. Maximum tensions of the fast motor units were lower than mean maximum tensions of control, whereas the S motor unit remained within the range observed in controls. In general, the isometric contractile properties, as well as fatigability, were within the ranges for each of the motor unit types in control cats. The mean fibre cross-sectional areas of the fibres within the FR and FF motor units were approximately 40 and 50% smaller than control, while the mean fibre size of the fibers within the S motor unit was similar to control. 4. Innervation ratios and specific tensions for all experimental motor units were within the ranges of those reported for tibialis anterior motor units in control cats. Thus, it appears that the decrease in maximum tension of the fast motor units was primarily related to a reduction in fibre size. 5. The spatial distribution of the fibres within fast motor units of a spinally isolated cat, as measured by interfibre distances of the motor unit fibres, was similar to that reported for control tibialis anterior motor units. 6. These data suggest that factors independent of activity play a prominent, if not dominant, role in maintaining the complement of motor unit types typical of adult cat muscles. In addition, normal innervation patterns appear to be maintained in the absence of activity.

Patterns of hair cell survival and innervation in the cochlea of the Bronx waltzer mouse

A massive loss of inner hair cells typifies the cochleae of Bronx waltzer mutant mice. We have characterized the surviving inner hair cells and their modified innervation by immunocytochemistry using antibodies against neuron-specific enolase, with additional stains for neural cell adhesion molecule and neurofilaments, and by electron microscopy. The surviving inner hair cells vary in size, neuron-specific enolase content and innervation. All neuron-specific enolase-positive cells are innervated by neuron-specific enolase-positive endings. There is apparent correspondence between the neuron-specific enolase immunoreactivity of sensory cells and their innervation. Well-stained cells are richly innervated (and large) while lightly stained cells received fewer nerve endings. Neuron-specific enolase-negative inner hair cells innervated either by neuron-specific enolase-positive or -negative nerve endings are very rare. Ultrastructurally, the surviving inner hair cells vary from those of a normal morphological appearance to underdeveloped or vacuolated. Most of the apparently normal inner hair cells are associated with few nerve endings; instead nerve growth cones are abundant in the adjacent inner spiral sulcus epithelium. Cells forming ribbon synapses with afferent endings are rare. The contingent of efferent endings in the inner spiral bundle depends on the presence of afferent endings. The absence of inner hair cells and the uneven distribution of nerve endings on the surviving cells results in the disruption of normal innervation patterns, especially in the thinning out or discontinuation of the inner spiral bundle and an uneven distribution of tunnel fibres. We infer that the sprouting of nerve endings and their convergence on a selected population of the surviving inner hair cells represents a compensatory regenerative phenomenon in response to the loss and the genetic defect of the remaining inner hair cells.

Retinoic acid potentiates the neurotrophic but not the mitogenic action of the class 1 heparin-binding growth factor (HBGF-1)

Retinoic acid promotes the neuronal survival properties of the class 1 heparin-binding growth factor (HBGF-1) on 8-day-old chick ciliary and sensory neurones. It has little or no effect on the survival promoting properties of class 2 heparin-binding growth factor (HBGF-2) on these cell types. Nerve growth factor (NGF) promoted survival of sympathetic and sensory neurones, and was unaffected at any concentration of retinoic acid. The mitogenic effect of both HBGF-1 and HBGF-2 was unaltered at any concentration of retinoic acid. It is suggested that naturally occurring gradients of retinoic acid, for example, as occur in the developing limb bud, could have a role in the development of normal innervation patterns through selective interaction with neurotrophic molecules.

Neurotoxicity of MDMA and Related Compounds: Anatomic Studiesa

The cytotoxic effects of amphetamine derivatives were studied by immunocytochemistry to identify the cellular compartments affected by these drugs, to obtain morphologic evidence of neuronal degeneration, and to assess the potential for regeneration. The substituted amphetamines, MDA, MDMA, PCA, and fenfluramine, all release serotonin and cause acute depletion of 5-HT from most axon terminals in forebrain. (1) Unequivocal signs of axon degeneration were seen at 36-48 hour survivals: 5-HT axons exhibited increased caliber, huge, swollen varicosities, fragmentation, and dilated proximal axon stumps. (2) Fine 5-HT axon terminals were persistently lost after drug administration, while beaded axons and raphe cell bodies were spared. These two types of 5-HT axons, which arise from separate raphe nuclei and form distinct ascending projections, are differentially vulnerable to psychotropic drugs. (3) From 2-8 months after treatment, there was progressive serotonergic re-innervation of neocortex along a fronto-occipital gradient. Longitudinal 5-HT axons grew into layers I and VI from rostral to caudal, before sprouting into middle cortical layers; this bilaminar pattern of growth simulates perinatal development of 5-HT innervation. This study demonstrates differential vulnerability of 5-HT projections, evidence for axonal degeneration, and sprouting of 5-HT axons leading to re-innervation of forebrain. While the sprouting axons are anatomically similar to the type that was damaged, it is not known whether a normal pattern of innervation is re-established.

Septohippocampal cholinergic axonal regeneration through peripheral nerve bridges: Quantification and temporal development

Axons of the adult mammalian CNS have been shown to regrow vigorously into peripheral nerve grafts. Using a cholinergic septohippocampal model for adult CNS regeneration, involving complete denervation of the hippocampal formation from its basal forebrain cholinergic afferents, this study has established quantitative parameters and a temporal baseline of cholinergic fiber regeneration into the dorsal hippocampal tissue through a peripheral sciatic nerve graft. In nerve-implanted animals (i) the nerve grafts are maximally invaded by AChE-positive fibers between 2 weeks and 1 month postlesion, (ii) the fibers entering the hippocampal formation from the graft show a peak numerical increase and rate of elongation around the first month and/or in the proximal hippocampal region, (iii) an apparently normal innervation pattern and fiber density in the most rostral 1.5 mm of the dorsal hippocampal formation is reached by 6 months postlesion. The present study provides a basis for future quantitative comparisons of manipulations of different components of the system, e.g., the contributing neurons, the bridging material, and the receiving central nervous tissue. The temporal/spatial pattern of fiber regeneration suggests that the hippocampal CNS tissue can be a good axonal growth-promoting environment, albeit with temporal and/or spatial limitations, and is therefore not an immutably restrictive environment for axonal regeneration.

Experimental american trypanomiasis in rats: sympathetic denervation, parasitism and inflammatory process

Tissue parasitism, inflammatory process (histologic methods) and sympathetic denervation (glyoxylic acid-induced histofluorescence for demonstration of catecholamines) were studied in the heart (atrium and ventricle) and the submandibular gland of rats infected with the Y strain of Trypanosoma cruzi. In the heart paralleling intense parasitism and inflammatory process, the sympathetic denervation started at day-6 of infection and at the end of the acute phase (day 20) practically no varicose nerve terminals were found in both myocardium and vessels. In the submandibular gland, in spite of the rarity of amastigote pseudocysts and the scarcity of inflammatory foci, slight to moderate (days 13-15 of infection) or moderate to severe denervation (day 20) was found. At day 120 of infection both organs exhibited normal pattern of sympathetic innervation and only the heart showed some inflammatory foci and rare pseudocysts (ventricle). Our data suggest the involvement of circulating factors in the sympathetic denervation phenomena but indicate that local inflammatory process is, at least, an aggravating factor.

Topographically selective reinnervation of adult mammalian skeletal muscles

In 2 rat muscles, serratus anterior and the diaphragm, the rostrocaudal axis of the motor pool is mapped onto the rostrocaudal axis of the muscle's surface (Laskowski and Sanes, 1987a). One possible basis for this orderly topography is that motor axons and intramuscular structures bear labels that favor connectivity among positionally matched partners. To test for the existence of such labels, we asked whether axons would selectively reinnervate appropriate portions of the muscles following nerve transection. We found that, on average, rostral and caudal halves of each muscle were preferentially reinnervated by axons from the rostral and caudal halves of its motor pool, respectively. In the serratus anterior, reinnervation was more selective following denervation in neonates than following denervation in adults, although in neither case was the normal pattern of innervation reestablished completely. These results show that motor axons can selectively reinnervate adult rat muscles, and support the idea that positional cues play a role in organizing neuromuscular topography.

Innervation of muscle receptors in the cross‐reinnervated soleus muscle of the cat

It has recently been reported (Gregory et al., J. Physiol., 331:367-383, 1982) that cutting a muscle nerve and letting it grow back into the muscle or cross-uniting the muscle with a foreign nerve results in major disruption of the normal response patterns of muscle spindles and tendon organs. Here we report observations on the structure of muscle receptors in cross-reinnervated and self-reinnervated soleus muscles in an attempt to detect abnormalities that might account for their disturbed function. Eight soleus muscles were reinnervated with the extensor digitorum longus nerve for periods up to 449 days and two were self-reinnervated. Following the physiological investigation, the muscle was fixed and stained according to the method of Barker and Ip (J. Physiol., 69:73P-74P, 1963). Spindles and tendon organs were teased from the muscle and photographed. In one cross-reinnervated muscle an attempt was made to isolate all receptors. About two-thirds of the normal number of spindles and tendon organs were found. Three categories of receptor were identified: normal, abnormal, and those having no visible nerve endings. There appeared to be little difference in degree of abnormality of receptors in self- and cross-reinnervated muscles. Of the 180 spindles, 3% were normal, 43% had no visible endings, and 54% had abnormal endings. Of 80 tendon organs, 38% were normally innervated, 33% were without visible innervation, and 29% had abnormal endings. We conclude that following long-term cross-reinnervation and self-reinnervation of soleus there is extensive disruption of the normal innervation pattern of both spindles and tendon organs which could account for their functional abnormalities.

Histochemical Assessment of the Intrinsic Innervation of the Normal Urinary Bladder (With 1 color plate)

In order to assess the normal intrinsic innervation pattern, an enzyme histochemical acetylcholinesterase and two immunohistochemical (S100 protein and neurofilaments) stainings were done on 38 normal urinary bladder specimens. The nerve density was calculated as a mean number of nerve fibers counted per high power field. S100 staining after adequate fixation proved to be similar to the acetylcholinesterase technique, avoids freezing manipulation, is easier to read and permits normal conventional histological examination. Neuropathology of bladder biopsies is an easily available diagnostic method in current neurourological practice.

Specific and nonspecific regeneration of motor axons after sciatic nerve injury and repair in the rat

The pattern of motor axon regeneration following unilateral sciatic nerve lesions (freezing or transection) was studied in adult rats. Transected nerves were repaired with epineurial or fascicular sutures. Four months after the lesion, the motor neuron cell body localization in the spinal cord of plantar or common peroneal nerve axons were examined bilaterally with retrograde transport of horseradish peroxidase. Motor neuron cell body localization was similar bilaterally after freezing, indicating that regenerating axons had reached their original peripheral innervation territory. However, after nerve transection, irrespective of whether epineurial or fascicular sutures were used, motor neuron cell body distribution on the operated side was abnormal with numerous labeled cell bodies located outside the area of the normal motor neuron pool. This finding indicates that after nerve transection the normal pattern of motor axon innervation is not restored even after fascicular nerve repair.

Cell suspension grafts of noradrenergic locus coeruleus neurons in rat hippocampus and spinal cord: Reinnervation and transmitter turnover

Fetal noradrenergic neurons from the brain stem locus coeruleus region can be successfully grafted as a dissociated cell suspension provided that the dissociation is done in the absence of any trypsin digestion step. The survival, fiber outgrowth and biochemical function of locus coeruleus neurons, taken from 13- to 15-day-old rat embryos, have been studied after injection into the dorsal hippocampal formation and the thoracolumbar spinal cord in adult rats. All rats were treated with an i.v. injection of 6-hydroxydopamine prior to grafting to remove the intrinsic locus coeruleus projections to these areas, and they were taken for fluorescence histochemical or biochemical analyses 2–7 months after transplantation. Up to 330 surviving noradrenaline neurons were found at each implantation site (injected with 2–3 μl of cell suspension) which represents an estimated survival rate of about 40%. In the most successful cases the entire dorsal hippocampal formation, and an approximately 4 cm long segment of the thoracolumbar spinal cord, was supplied with a new noradrenaline-containing terminal network, which reached normal densities in the regions closest to the grafts. In the hippocampal formation, in particular, the ingrowing axons re-established a laminar innervation pattern which resembled that of the normal locus coeruleus afferents. In the hippocampus, two 2-μl injections of locus coeruleus cell suspension restored the total hippocampal noradrenaline content to an average of 55%, and the noradrenaline synthesis rate (as assessed by the rate of DOPA accumulation after synthesis inhibition) was found to be close to normal in the graft-reinnervated specimens. In the spinal cord, two 3-μl injections restored the noradrenaline level in the thoracolumbar cord (a 4.5 cm long segment) to an average of 22% of normal, with the highest individual levels being close to normal. Determinations of the noradrenaline metabolite 3,4-dihydroxy-phenylethyleneglycol indicated that the rate of noradrenaline metabolism in the graftreinnervated spinal cord was close to that of the normal intact spinal cord. The results demonstrate the potential of the suspension grafting technique for extensive noradrenergic reinnervation of the hippocampal formation or large portions of the spinal cord. Fetal locus coeruleus neurons implanted in this way can re-establish fairly normal terminal innervation patterns and reinstate noradrenaline turnover and metabolism in a previously denervated central target.

Age-related structural investigation of the Bronx waltzer mutant mouse cochlea: scanning and transmission electron microscopy.

Cochleas of mice homozygous for the Bronx waltzer gene (symbol bv) were investigated using scanning (SEM) and transmission (TEM) electron microscopy. An age-related study was done from birth to postnatal day 100. With SEM, the arrangement of hair cells confirmed the unique feature of the bv/bv cochlea: the inner hair cells (IHCs) were either absent or abnormally haired but the outer hair cells (OHCs) appeared normal. No significant difference was observed with age. Using TEM, the remaining (20-25%) IHCs could be divided into two groups: normal-looking IHCs but with an abnormal synaptic pole, and abnormal, abortive-like IHCs. Very little if any sign of degeneration was observed whatever the age. OHCs displayed an almost normal cytology and pattern of innervation. The neurons of the spiral ganglion were very rare, even at birth. These findings suggest that the bv mutation should rather be classified in another group, than 'degenerative'. The persistence of normal structures at OHC level is discussed in light of the cochlear physiology of the bv/bv: it again raises the question of the real role of OHCs in the peripheral auditory mechanisms.

Distribution and quantification of ACh receptors and innervation in diaphragm muscle of normal and mdg mouse embryos

Muscular dysgenesis ( mdg) in the mouse is an autosomal recessive mutation, expressed in the homozygous state ( in vivo and in vitro) as an absence of skeletal muscle contraction. The distribution of acetylcholine receptors (ACh R) in the diaphragms of phenotypically normal and dysgenic ( mdg mdg ) embryos was studied from the 14th to 19th day of gestation by binding of 125I-α-bungarotoxin to the muscle, followed by autoradiography of longitudinally sectioned hemidiaphragms and/or of isolated muscle fibers. Localization of ACh R at putative motor end-plate regions begins 14 to 15 days in utero in both normal and dysgenic diaphragms. The distribution of high ACh R density patches is aberrantly scattered beyond the normal innervation pattern in dysgenic diaphragms. Isolated mutant fibers possess (1) multiple ACh R clusters, up to five per single fiber, (2) larger clusters of more variable morphology and variable receptor density than normal clusters, and (3) higher levels of extrajunctional receptors than normal fibers. These autoradiographic results correlate well with higher total level of toxin binding sites per diaphragm and per milligram protein in dysgenic vs normal muscle, as quantified from γ counting of sucrose density gradient isolation of 125I-toxin-ACh R complexes. The dispersed distribution of ACh R patches on dysgenic muscle may be correlated with extensive phrenic nerve branching as demonstrated by silver impregnation technique. We suggest that the aberrant ACh R cluster distribution is a result of multiple innervation of single fibers from the branched nerve terminals. Possible causes of the excessive nerve branching in the mutant are discussed in light of generalized nerve sprouting found in paralyzed muscle.

Changes in acetylcholinesterase-positive nerves of the submandibular salivary gland during experimental infection with a protozoon, Trypanosoma cruzi, in rats

Using a thiocholine acetylcholinesterase histochemical technique, an appreciable reduction of the innervation was demonstrated in the submandibular glands of rats inoculated with the Y strain of Trypanosoma cruzi, at the early chronic phase of the infection. During the chronic phase of the disease there was recovery of the normal pattern of innervation in all infected animals.

Local and systemic effects of tetrodotoxin on the formation and elimination of synapses in reinnervated adult rat muscle.

1. Polyneuronal innervation of normal and reinnervated fourth deep lumbrical muscle fibres was studied with tension measurements and intracellular recordings. From the tenth day after a complete crush of the muscle nerve, some of the reinnervated muscles were completely paralysed for up to 15 days by local application of tetrodotoxin (TTX) to the sciatic nerve. Other animals received only systemic infusion of TTX during the muscle reinnervation.2. Measurements of tetanic-tension overlap suggested that about 6% of the muscle fibres in the normal lumbrical muscle were polyneuronally innervated, while intracellular recordings suggested that the percentage was as high as 25%. This discrepancy was mainly due to the presence of one small, sub-threshold end-plate potential (e.p.p.) and one large, suprathreshold e.p.p. in almost all polyneuronally innervated muscle fibres.3. Intracellular recordings during muscle reinnervation showed that the extent of polyneuronal innervation reached a maximum of 50% 10-15 days after denervation and that by 16-20 days this had decreased to a level similar to that found in normal muscle.4. After a week of total muscle paralysis the extent of polyneuronal innervation had increased to about 80%, estimated by both tension measurements and intracellular recordings. Subsequently, there was no sign of any net elimination of the polyneuronal innervation, even in muscles paralysed for up to two weeks. Many of the polyneuronally innervated fibres were innervated by at least two motor axons. each producing suprathreshold e.p.p.s.5. In muscles contralateral to the paralysed muscles, the extent of polyneuronal innervation reached a maximum of 50% 10-15 days after denervation as in reinnervated muscles not exposed to TTX. But in contrast to the subsequent decrease in the extent of polyneuronal innervation in animals which received no TTX, this level of polyneuronal innervation persisted in muscles contralateral to the paralysed muscles. The same was true for reinnervated muscles in animals which only received TTX systemically.6. The increased level of polyneuronal innervation after TTX application was not caused by differences in the number of motor units or in number of muscle fibres.7. Paralysed muscles relaxed much more slowly than non-paralysed muscles at the end of a fused tetanic contraction. The tetanus/twitch ratio of these muscles was also smaller than in contralateral control muscles and the rise time of the twitch was greater.8. It is concluded that a substantial fraction of the fibres in the normal lumbrical muscle of young rats is polyneuronally innervated. After reinnervation, the normal innervation pattern is re-established, but no net elimination of the polyneuronal innervation occurs unless either nerve or muscle or both are active. A net elimination of synapses is also prevented when TTX is present systemically in low concentrations.

Ascending projections to the inferior colliculus following unilateral cochlear ablation in the neonatal gerbil, Meriones unguiculatus.

We evaluated the consequences of neonatal cochlear destruction upon ascending projections to the inferior colliculi. Unilateral cochlear ablations were performed in both neonatal and adult gerbils. Four to 12 months later, the inferior colliculus (IC) was examined physiologically and injected unilaterally with horseradish peroxidase (HRP). The number of labeled cells was determined bilaterally in all three divisions of cochlear nucleus (CN) and in the medial superior olive (MSO). In both experimental groups, transneuronal changes within the deafferented CN were greater in the ventral divisions than in the dorsal division. On the unoperated side the magnitude of projections from CN to the inferior colliculi was altered in animals lesioned as neonates. Following HRP injections into the IC on the unoperated side, the number of ipsilaterally labeled cells in CN (unoperated side) was significantly greater in the neonatal experimental group than in adult experimental and control animals. These anatomical changes were accompanied by increased ipsilaterally evoked excitatory activity recorded in the IC on the unoperated side. Following HRP injections into the IC on the ablated side, the number of contralaterally labeled cells in CN (unoperated side) was significantly reduced in animals lesioned as neonates as compared with control animals. The number of labeled cells in ipsilateral MSO was not significantly different across groups. Our interpretation is that unilateral cochlear ablation in neonatal gerbils results in an increase in the magnitude of ipsilateral projections and a decrease in the magnitude of contralateral projections from CN on the unoperated side to the inferior colliculi. These data suggest that the normal pattern of innervation of the IC results, in part, from interactions among afferent projections.