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H Colman

Publications and source records attributed to H Colman.

9 recordsLinked to original sources
PubMed1998

Synaptic competition during the reformation of a neuromuscular map.

We have been studying the mechanisms whereby pools of motor neurons establish a rostrocaudal bias in the position of their synapses in some skeletal muscles. The serratus anterior (SA) muscle of the rat displays a rostrocaudal topographic map before birth, and the topography is re-established after denervation. In this report, we explore the potential role of synaptic competition between innervating axons as a means of generating topographic specificity. We followed the progress of the reformation of this map in neonatal animals under conditions that enhanced the likelihood of observing synaptic competition. This was accomplished by forcing caudal axons to regenerate ahead of rostral axons onto a surgically reduced SA muscle. In this way, caudal (C7) motor neurons had unopposed access to vacated synaptic sites on the remaining rostral half of the SA before the return of the rostral (C6) axons. Intracellular recording revealed that 2 d after the second denervation, most of the reinnervated end plates contained only axons from the C7 branch; the remaining reinnervated end plates received input from C6 only or were multiply innervated by C6 and C7 axons. After 6 d, the pattern was reversed, with most end plates innervated exclusively by C6. After 17 d, axons from C6 were the sole input to reinnervated end plates. During the transition from C7- to C6-dominated input, at end plates coinnervated by C6 and C7 axons, the average quantal content from C6 was the same as that from C7; after 7 d, the quantal content of C6 was greater than that of C7. We have thus developed an experimental situation in which the outcome of synaptic competition is predictable and can be influenced by the positional labels associated with axons from different levels in the spinal cord.

Animals↗
PubMed1997

Alterations in synaptic strength preceding axon withdrawal.

Permanent removal of axonal input to postsynaptic cells helps shape the pattern of neuronal connections in response to experience, but the process is poorly understood. Intracellular recording from newborn and adult mouse muscle fibers temporarily innervated by two axons showed an increasing disparity in the synaptic strengths of the two inputs before one was eliminated. The connection that survived gained strength by increasing the amount of neurotransmitter released (quantal content), whereas the input that was subsequently removed became progressively weaker, because of a reduction in quantal content and a reduction in quantal efficacy associated with reduced postsynaptic receptor density. Once the synaptic strengths of two inputs began to diverge, complete axonal withdrawal of the weaker input occurred within 1 to 2 days. These experiments provide a link between experience-driven changes in synaptic strength and long-term changes in connectivity in the mammalian nervous system.

Acetylcholine↗
PubMed1994

In vivo imaging shows loss of synaptic sites from neuromuscular junctions in a model of myasthenia gravis.

We examined the pre- and postsynaptic elements of the neuromuscular junction during immune attack on the postsynaptic acetylcholine receptors (AChRs) in a model of myasthenia gravis (MG). We followed, in the sternomastoid muscle of living mice, the staining of nerve terminals and postsynaptic AChRs at individual neuromuscular junctions in situ for up to 16 days after exposure to a monoclonal anti-AChR antibody. Several exposures to this antibody over 6 days led to spotty loss of AChR staining 1 to 3 days later within individual neuromuscular junctions. In addition, we observed loss of motor nerve terminal staining at presynaptic sites opposed to postsynaptic regions that had lost AChRs. Sites that lost pre- and postsynaptic staining were often immediately adjacent to other junctional regions that maintained a high density of AChRs and still stained presynaptically. Ultimately, the loss of synaptic sites resulted in neuromuscular junctions that appeared to be abnormally fragmented. To determine whether junctions recovered from the immune attack, we followed some antibody-treated muscle fibers for an additional 8 days without further exposure to antibody. Signs of recovery were evident because some of the synaptic regions that had previously lost AChRs subsequently regained them. But these junctions still remained fragmented both pre- and postsynaptically. These findings suggest that the postsynaptic membrane is affected in a highly local way by the immune attack on AChRs occurring in MG. One consequence of this attack is a long-term loss of not only postsynaptic components but also the overlying nerve terminals.

Animals↗
PubMed1993

Interactions between nerve and muscle: synapse elimination at the developing neuromuscular junction.

Studies of synaptogenesis at the developing neuromuscular junction have provided a wealth of information regarding the various mechanisms that are involved in the formation of synaptic connections. In addition to synapse formation, however, the mature pattern of innervation at the neuromuscular junction (and elsewhere in the nervous system) depends on a significant loss of synaptic connections during development. The molecular mechanisms involved in the process of synapse elimination are not understood. Recent work at the neuromuscular junction suggests that changes in the postsynaptic cell may be necessary in order for nerve terminals to be eliminated. Thus, in contrast to synapse formation in which an axon terminal initiates a cascade of changes leading to the formation of pre- and postsynaptic specializations, synapse elimination may be initiated by local changes in the postsynaptic cell that disassemble the postsynaptic apparatus and ultimately remove the overlying terminal. In this review, we wish to examine the potential role that some of the factors involved in synapse formation might play in the less-well-understood phenomenon of synapse elimination.

Aging↗
PubMed1990

Binocular competition in the control of geniculate cell size depends upon visual cortical N-methyl-D-aspartate receptor activation.

The lateral geniculate nucleus relays visual information from the retina to cortex. One well-known anatomical consequence of monocular deprivation during early postnatal development is a shrinkage of neurons in the lamina of the lateral geniculate nucleus that receive input from the deprived eye. This is thought to reflect the competition of afferents subserving the two eyes, possibly at the level of the visual cortex. We find that blockade of N-methyl-D-aspartate receptors in kitten visual cortex disrupts this process of binocular competition. These data provide direct evidence that postsynaptic activation of cortical neurons is required for competitive changes in lateral geniculate cell size and suggest a role for N-methyl-D-aspartate receptors in anatomical as well as physiological plasticity in the mammalian visual system.

2-Amino-5-phosphonovalerate↗
PubMed1990

An orally administered opiate blocker, naltrexone, attenuates self-injurious behavior.

Several recent reports have indicated that opioid blockers are effective in attenuating self-injurious behavior (SIB). In the present study, four patients with SIB were challenged with four fixed doses (0, 25, 50, 100 mg) of naltrexone. In a double-blind procedure, all patients received each dose on a different week as determined by latin square design. Naltrexone was given on Monday and Wednesday of each week, and patients were videotaped daily for 10 minutes in the morning and afternoon. The tapes were scored for incidents of SIB, stereotypy, and activity, with interrater reliability of 0.93. The Conners Teacher Rating Scale was administered by staff in the morning and afternoon each day. The Vineland was completed each week (Thursday). All patients had decreased SIB when treated with naltrexone. Three patients decreased their SIB as dose of naltrexone increased. There were no consistent effects of naltrexone on stereotypy, activity, or performance on the Conners or the Vineland. These results suggest that endogenous opioids are implicated in SIB and that naltrexone is a powerful tool for examination of this treatment-resistant behavior.

Adult↗