Compensation in the number of presynaptic dense projections and synaptic vesicles in remaining parallel fibres following cerebellar lesions

Hillman, Dean E.; Chen, S.

doi:10.1007/bf01200804

Cited by 30 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since this increase was not seen in all groups where one might have anticipated it, we do not wish to overinterpret these results. Nonetheless, previous research has shown that age-related (Jones, 1988) and lesion-induced (Anthes et al, 1993;Chen and Hillman, 1985;Hillman and Chen, 1985) reductions in synaptic number are also accompanied by an elongation of the remaining synapses. Increasing synaptic length may reflect an attempt to maintain a constant level of synaptic transmission in a neural pathway that has fewer synaptic contacts.…”

Section: Nmda Antagonist-induced Alterations In Synaptic Lengthmentioning

confidence: 97%

Effect of chronic administration of NMDA antagonists on synaptic development

Brooks

Petit

LeBoutillier

1997

Synapse

View full text Add to dashboard Cite

The current research assessed the role of the N-methyl-D-aspartate (NMDA) receptor in developmental synaptic plasticity. This was accomplished by quantitative analysis of synaptic number and morphology following pharmacological manipulation of NMDA receptor activity using either the competitive antagonist 2-amino-5-phosphonovaleric acid (APV) or the noncompetitive antagonist phencyclidine (PCP). In the first group, 15-day-old male Long-Evans rats were implanted with osmotic minipumps, which administered 50 mM APV or vehicle at a rate of 0.5 microliter per h into the subjects' occipital cortex for 14 days. At age 30 days (P30), the rats were sacrificed and their occipital neocortices were examined. A second group of rats was given subcutaneous injections of 10 mg/kg PCP or vehicle once daily beginning on P5 for a period of 15 days, and was sacrificed on P20. To determine the effects following withdrawal from long-term NMDA antagonism, a third group of animals was given the same PCP injection routine until P20, but was sacrificed on P21, P26, P36, and P56. Developmental administration of APV was associated with a decreased molecular layer depth and estimated total number of synapses. Similarly, PCP induced a reduction in brain weight, molecular layer depth, and estimated total number of synapses. Withdrawal from NMDA antagonism was initially associated with similar results, i.e., reduced brain weight, cortex depth, synaptic density, and estimated total number of synapses, along with an increase in synaptic length. By P36, however, there was a transitory rebound associated with increased molecular layer depth and estimated total number of synapses. These results support the suggestion that NMDA receptor activation is integral to naturally occurring developmental synaptogenesis, and underscore the importance of NMDA receptor involvement in the process of synaptic plasticity.

show abstract

Section: Nmda Antagonist-induced Alterations In Synaptic Lengthmentioning

confidence: 97%

Effect of chronic administration of NMDA antagonists on synaptic development

Brooks

Petit

LeBoutillier

1997

Synapse

View full text Add to dashboard Cite

show abstract

“…Experimental studies highlight the powerful compensatory properties of the brain following a cerebellar lesion. Thanks to a large repertoire of plastic mechanisms within the cerebellar circuitry itself especially at the cerebellar cortical level, compensation also involves purely local responses in the cerebellar cortex and in cerebellar nuclei [33]. Cerebellum is also recruited in the mechanism of compensation after an extracerebellar injury, including for lesions of the peripheral nervous system such as transection of nerves [14].…”

Section: The Compensation Following Transection Of Cerebellar Pedunclesmentioning

confidence: 99%

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders

et al. 2019

View full text Add to dashboard Cite

Cerebellar reserve refers to the capacity of the cerebellum to compensate for tissue damage or loss of function resulting from many different etiologies. When the inciting event produces acute focal damage (e.g., stroke, trauma), impaired cerebellar function may be compensated for by other cerebellar areas or by extracerebellar structures (i.e., structural cerebellar reserve). In contrast, when pathological changes compromise cerebellar neuronal integrity gradually leading to cell death (e.g., metabolic and immune-mediated cerebellar ataxias, neurodegenerative ataxias), it is possible that the affected area itself can compensate for the slowly evolving cerebellar lesion (i.e., functional cerebellar reserve). Here, we examine cerebellar reserve from the perspective of the three cornerstones of clinical ataxiology: control of ocular movements, coordination of voluntary axial and appendicular movements, and cognitive functions. Current evidence indicates that cerebellar reserve is potentiated by environmental enrichment through the mechanisms of autophagy and synaptogenesis, suggesting that cerebellar reserve is not rigid or fixed, but exhibits plasticity potentiated by experience. These conclusions have therapeutic implications. During the period when cerebellar reserve is preserved, treatments should be directed at stopping disease progression and/or limiting the pathological process. Simultaneously, cerebellar reserve may be potentiated using multiple approaches. Potentiation of cerebellar reserve may lead to compensation and restoration of function in the setting of cerebellar diseases, and also in disorders primarily of the cerebral hemispheres by enhancing cerebellar mechanisms of action. It therefore appears that cerebellar reserve, and the underlying plasticity of cerebellar microcircuitry that enables it, may be of critical neurobiological importance to a wide range of neurological/neuropsychiatric conditions.

show abstract

“…Synaptic structure is plastic (Bailey and Kandel, 1993;Chen and Hillman, 1990;Hillman and Chen, 1985), with, for example, junctions going from being regions of flat apposition to concave or invaginated structures, as a function of prior activity (Desmond and Levy, 1986b;Fields and Ellisman, 1985;Fields et al, 1987;Petit et al, 1989). Also, the length of the contact zone is modifiable (Hillman and Chen, 1985;Chen and Hillman, 1990). We therefore tested the effects of several parameters: 1) contact zone radius, 2) number of receptor molecules, which is determined by receptor disk radius and surface density of the receptor molecules (see Methods: Receptor distribution), and 3) number of transmitter molecules released from a vesicle.…”

Section: Substrates For Synaptic Plasticitymentioning

confidence: 99%

The effects of geometrical parameters on synaptic transmission: a Monte Carlo simulation study

Kruk¹,

Korn²,

Faber³

1997

Biophysical Journal

View full text Add to dashboard Cite

Monte Carlo simulations of transmitter diffusion and its interactions with postsynaptic receptors have been used to study properties of quantal responses at central synapses. Fast synaptic responses characteristic of those recorded at glycinergic junctions on the teleost Mauthner cell (time to peak approximately 0.3-0.4 ms and decay time constant approximately 3-6 ms) served as the initial reference, and smaller contacts with fewer postsynaptic receptors were also modeled. Consistent with experimental findings, diffusion, simulated using a random walk algorithm and assuming a diffusion coefficient of 0.5-1.0 x 10(-5) cm2 s(-1), was sufficiently fast to account for transmitter removal from the synaptic cleft. Transmitter-receptor interactions were modeled as a two-step binding process, with the double-bound state having opened and closed conformations. Addition of a third binding step only slightly decreased response amplitude but significantly slowed both its rising and decay phases. The model allowed us to assess the sources of response variability and the likelihood of postsynaptic saturation as functions of multiple kinetic and spatial parameters. The method of nonstationary fluctuation analysis, typically used to estimate the number of functional channels at a synapse and single channel current, proved unreliable, presumably because the receptors in the postsynaptic matrix are not uniformly exposed to the same profile of transmitter concentration. Thus, the time course of the probability of channel opening most likely varies among receptors. Finally, possible substrates for phenomena of synaptic plasticity, such as long-term potentiation, were explored, including the diameter of the contact zone, defined by the region of pre- and postsynaptic apposition, the number and distribution of the receptors, and the degree of vesicle filling. Surprisingly, response amplitude is quite sensitive to the size of the receptor-free annulus surrounding the receptor cluster, such that expansion of the contact zone could produce an appreciable increase in quantal size, normally attributed to either the presence of more receptors or the release of more transmitter molecules.

show abstract

Compensation in the number of presynaptic dense projections and synaptic vesicles in remaining parallel fibres following cerebellar lesions

Cited by 30 publications

References 27 publications

Effect of chronic administration of NMDA antagonists on synaptic development

Effect of chronic administration of NMDA antagonists on synaptic development

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders

The effects of geometrical parameters on synaptic transmission: a Monte Carlo simulation study

Contact Info

Product

Resources

About