Muscarinic Modulation of Recruitment Threshold and Firing Rate in Rat Oculomotor Nucleus Motoneurons

Nieto-González, José Luis; Carrascal, Livia; Nuñez-Abades, Pedro; Torres, Blas

doi:10.1152/jn.90239.2008

Cited by 19 publications

(14 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is widely accepted that synaptic circuitry, Mn excitability and extraocular muscles mature jointly. The patterns of oculomotor Mn-specific activity may be determinant for muscle fiber phenotype, as reported in spinal Mns [53]; motor units are refined during postnatal development strengthening some synapse and eliminating others [47]; muscle-derived factors (neurotrophins) are essential for neuronal survival during development and their range of actions support the phasic and tonic activities of Mns in conducting eye movement [54]; lastly, synaptic inputs to Mns play an important role in determining recruitment threshold [52], [55]. With postnatal development, more active Mns have competitive advantages in muscle synaptic refinement [47], [56].…”

Section: Discussionmentioning

confidence: 99%

Diminution of Voltage Threshold Plays a Key Role in Determining Recruitment of Oculomotor Nucleus Motoneurons during Postnatal Development

et al. 2011

Self Cite

View full text Add to dashboard Cite

The size principle dictates the orderly recruitment of motoneurons (Mns). This principle assumes that Mns of different sizes have a similar voltage threshold, cell size being the crucial property in determining neuronal recruitment. Thus, smaller neurons have higher membrane resistance and require a lower depolarizing current to reach spike threshold. However, the cell size contribution to recruitment in Mns during postnatal development remains unknown. To investigate this subject, rat oculomotor nucleus Mns were intracellularly labeled and their electrophysiological properties recorded in a brain slice preparation. Mns were divided into 2 age groups: neonatal (1–7 postnatal days, n = 14) and adult (20–30 postnatal days, n = 10). The increase in size of Mns led to a decrease in input resistance with a strong linear relationship in both age groups. A well-fitted inverse correlation was also found between input resistance and rheobase in both age groups. However, input resistance versus rheobase did not correlate when data from neonatal and adult Mns were combined in a single group. This lack of correlation is due to the fact that decrease in input resistance of developing Mns did not lead to an increase in rheobase. Indeed, a diminution in rheobase was found, and it was accompanied by an unexpected decrease in voltage threshold. Additionally, the decrease in rheobase co-varied with decrease in voltage threshold in developing Mns. These data support that the size principle governs the recruitment order in neonatal Mns and is maintained in adult Mns of the oculomotor nucleus; but during postnatal development the crucial property in determining recruitment order in these Mns was not the modifications of cell size-input resistance but of voltage threshold.

show abstract

Section: Discussionmentioning

confidence: 99%

Diminution of Voltage Threshold Plays a Key Role in Determining Recruitment of Oculomotor Nucleus Motoneurons during Postnatal Development

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…It also remains to be seen how upstream neuromodulators may affect microcircuit function. For example, acetylcholine and serotonin can activate or inhibit SST interneurons through direct and indirect (VIP-mediated) pathways (115, 116), which may drive brain state-dependent changes in microcircuit function (71, 117). …”

Section: A Pathophysiological Model Of Low Sst Cell Functionmentioning

confidence: 99%

Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives

Fee

Banasr

Sibille

2017

Biological Psychiatry

286

217

View full text Add to dashboard Cite

The functional integration of external and internal signals forms the basis of information processing and is essential for higher cognitive functions. This occurs in finely-tuned cortical microcircuits whose functions are balanced at the cellular level by excitatory glutamatergic pyramidal neurons and inhibitory γ-aminobutyric acid (GABA) interneurons. The balance of excitation and inhibition, from cellular processes to neural network activity, is characteristically disrupted in multiple neuropsychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BPD), anxiety disorders, and schizophrenia (SCZ). Specifically, nearly three decades of research demonstrate a role for reduced inhibitory GABA level and function across disorders. In MDD, recent evidence from human postmortem and animal studies suggests a selective vulnerability of GABAergic interneurons that co-express the neuropeptide somatostatin (“SST cells/interneurons”). Advances in cell type-specific molecular genetics have now helped to elucidate several important roles for SST interneurons in cortical processing (regulation of pyramidal cell excitatory input) and behavioral control (mood and cognition). Here, we review evidence for altered inhibitory function arising from GABAergic deficits across disorders, and specifically in MDD. We then focus on properties of the cortical microcircuit, wherein SST-positive GABA interneuron deficits may disrupt functioning in several ways. Finally, we discuss the putative origins of SST cell deficits, as informed by recent research, and implications for therapeutic approaches. We conclude that deficits in SST interneurons represent a contributing cellular pathology, and therefore a promising target for normalizing altered inhibitory function in MDD and other disorders with reduced SST cell and GABA functions.

show abstract

“…NGF has been shown to regulate excitability through several ionic currents (Zhang and Nicol, 2004;Luther and Birren, 2009). One of them is the M-current, likely present in oculomotor motoneurons, as seen with carbachol-induced depolarizations (Nieto-Gonzalez et al, 2009). This current is modulated via the two NGF receptors.…”

Section: Changes In the Motoneuronal Excitabilitymentioning

confidence: 99%

Nerve Growth Factor Regulates the Firing Patterns and Synaptic Composition of Motoneurons

Carrizosa¹,

Morado-Díaz²,

Morcuende³

et al. 2010

Journal of Neuroscience

View full text Add to dashboard Cite

Target-derived neurotrophins exert powerful synaptotrophic actions in the adult brain and are involved in the regulation of different forms of synaptic plasticity. Target disconnection produces a profound synaptic stripping due to the lack of trophic support. Consequently, target reinnervation leads to synaptic remodeling and restoration of cellular functions. Extraocular motoneurons are unique in that they normally express the TrkA neurotrophin receptor in the adult, a feature not seen in other cranial or spinal motoneurons, except after lesions such as axotomy or in neurodegenerative diseases like amyotrophic lateral sclerosis. We investigated the effects of nerve growth factor (NGF) by retrogradely delivering this neurotrophin to abducens motoneurons of adult cats. Axotomy reduced the density of somatic boutons and the overall tonic and phasic firing modulation. Treatment with NGF restored synaptic inputs and firing modulation in axotomized motoneurons. When K252a, a selective inhibitor of tyrosine kinase activity, was applied to specifically test TrkA effects, the NGF-mediated restoration of synapses and firing-related parameters was abolished. Discharge variability and recruitment threshold were, however, increased by NGF compared with control or axotomized motoneurons. Interestingly, these parameters returned to normal following application of REX, an antibody raised against neurotrophin receptor p75 (p75 NTR ). In conclusion, NGF, acting retrogradely through TrkA receptors, supports afferent boutons and regulates the burst and tonic signals correlated with eye movements. On the other hand, p75 NTR activation regulates recruitment threshold, which impacts on firing regularity. To our knowledge, this is the first report showing powerful synaptotrophic effects of NGF on motoneurons in vivo.

show abstract

Muscarinic Modulation of Recruitment Threshold and Firing Rate in Rat Oculomotor Nucleus Motoneurons

Cited by 19 publications

References 51 publications

Diminution of Voltage Threshold Plays a Key Role in Determining Recruitment of Oculomotor Nucleus Motoneurons during Postnatal Development

Diminution of Voltage Threshold Plays a Key Role in Determining Recruitment of Oculomotor Nucleus Motoneurons during Postnatal Development

Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives

Nerve Growth Factor Regulates the Firing Patterns and Synaptic Composition of Motoneurons

Contact Info

Product

Resources

About