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Jabeen S, Thirumalai V. The interplay between electrical and chemical synaptogenesis. J Neurophysiol 2018; 120:1914-1922. [PMID: 30067121 PMCID: PMC6230774 DOI: 10.1152/jn.00398.2018] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Neurons communicate with each other via electrical or chemical synaptic connections. The pattern and strength of connections between neurons are critical for generating appropriate output. What mechanisms govern the formation of electrical and/or chemical synapses between two neurons? Recent studies indicate that common molecular players could regulate the formation of both of these classes of synapses. In addition, electrical and chemical synapses can mutually coregulate each other’s formation. Electrical activity, generated spontaneously by the nervous system or initiated from sensory experience, plays an important role in this process, leading to the selection of appropriate connections and the elimination of inappropriate ones. In this review, we discuss recent studies that shed light on the formation and developmental interactions of chemical and electrical synapses.
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Affiliation(s)
- Shaista Jabeen
- National Centre for Biological Sciences, Tata Institute for Fundamental Research , Bangalore , India.,Manipal Academy of Higher Education, Madhav Nagar, Manipal , India
| | - Vatsala Thirumalai
- National Centre for Biological Sciences, Tata Institute for Fundamental Research , Bangalore , India
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2
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Zolnik TA, Connors BW. Electrical synapses and the development of inhibitory circuits in the thalamus. J Physiol 2016; 594:2579-92. [PMID: 26864476 PMCID: PMC4865577 DOI: 10.1113/jp271880] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 02/05/2016] [Indexed: 11/08/2022] Open
Abstract
KEY POINTS The thalamus is a structure critical for information processing and transfer to the cortex. Thalamic reticular neurons are inhibitory cells interconnected by electrical synapses, most of which require the gap junction protein connexin36 (Cx36). We investigated whether electrical synapses play a role in the maturation of thalamic networks by studying neurons in mice with and without Cx36. When Cx36 was deleted, inhibitory synapses were more numerous, although both divergent inhibitory connectivity and dendritic complexity were reduced. Surprisingly, we observed non-Cx36-dependent electrical synapses with unusual biophysical properties interconnecting some reticular neurons in mice lacking Cx36. The results of the present study suggest an important role for Cx36-dependent electrical synapses in the development of thalamic circuits. ABSTRACT Neurons within the mature thalamic reticular nucleus (TRN) powerfully inhibit ventrobasal (VB) thalamic relay neurons via GABAergic synapses. TRN neurons are also coupled to one another by electrical synapses that depend strongly on the gap junction protein connexin36 (Cx36). Electrical synapses in the TRN precede the postnatal development of TRN-to-VB inhibition. We investigated how the deletion of Cx36 affects the maturation of TRN and VB neurons, electrical coupling and GABAergic synapses by studying wild-type (WT) and Cx36 knockout (KO) mice. The incidence and strength of electrical coupling in TRN was sharply reduced, but not abolished, in KO mice. Surprisingly, electrical synapses between Cx36-KO neurons had faster voltage-dependent decay kinetics and conductance asymmetry (rectification) than did electrical synapses between WT neurons. The properties of TRN-mediated inhibition in VB also depended on the Cx36 genotype. Deletion of Cx36 increased the frequency and shifted the amplitude distributions of miniature IPSCs, whereas the paired-pulse ratio of evoked IPSCs was unaffected, suggesting that the absence of Cx36 led to an increase in GABAergic synaptic contacts. VB neurons from Cx36-KO mice also tended to have simpler dendritic trees and fewer divergent inputs from the TRN compared to WT cells. The findings obtained in the present study suggest that proper development of thalamic inhibitory circuitry, neuronal morphology, TRN cell function and electrical coupling requires Cx36. In the absence of Cx36, some TRN neurons express asymmetric electrical coupling mediated by other unidentified connexin subtypes.
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Affiliation(s)
- Timothy A Zolnik
- Department of Neuroscience, Division of Biology & Medicine, Brown University, Providence, RI, USA
- Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Barry W Connors
- Department of Neuroscience, Division of Biology & Medicine, Brown University, Providence, RI, USA
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Carrascal L, Nieto-González J, Pardillo-Díaz R, Pásaro R, Barrionuevo G, Torres B, Cameron WE, Núñez-Abades P. Time windows for postnatal changes in morphology and membrane excitability of genioglossal and oculomotor motoneurons. World J Neurol 2015; 5:113-131. [DOI: 10.5316/wjn.v5.i4.113] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 10/07/2015] [Accepted: 12/08/2015] [Indexed: 02/06/2023] Open
Abstract
Time windows for postnatal changes in morphology and membrane excitability of genioglossal (GG) and oculomotor (OCM) motoneurons (MNs) are yet to be fully described. Analysis of data on brain slices in vitro of the 2 populations of MNs point to a well-defined developmental program that progresses with common age-related changes characterized by: (1) increase of dendritic surface along with length and reshaping of dendritic tree complexity; (2) disappearance of gap junctions early in development; (3) decrease of membrane passive properties, such as input resistance and time constant, together with an increase in the number of cells displaying sag, and modifications in rheobase; (4) action potential shortening and afterhyperpolarization; and (5) an increase in gain and maximum firing frequency. These modifications take place at different time windows for each motoneuronal population. In GG MNs, active membrane properties change mainly during the first postnatal week, passive membrane properties in the second week, and dendritic increasing length and size in the third week of development. In OCM MNs, changes in passive membrane properties and growth of dendritic size take place during the first postnatal week, while active membrane properties and rheobase change during the second and third weeks of development. The sequential order of changes is inverted between active and passive membrane properties, and growth in size does not temporally coincide for both motoneuron populations. These findings are discussed on the basis of environmental cues related to maturation of the respiratory and OCM systems.
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Serrano-Velez JL, Rodriguez-Alvarado M, Torres-Vazquez II, Fraser SE, Yasumura T, Vanderpool KG, Rash JE, Rosa-Molinar E. Abundance of gap junctions at glutamatergic mixed synapses in adult Mosquitofish spinal cord neurons. Front Neural Circuits 2014; 8:66. [PMID: 25018700 PMCID: PMC4072101 DOI: 10.3389/fncir.2014.00066] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2014] [Accepted: 05/28/2014] [Indexed: 11/13/2022] Open
Abstract
"Dye-coupling", whole-mount immunohistochemistry for gap junction channel protein connexin 35 (Cx35), and freeze-fracture replica immunogold labeling (FRIL) reveal an abundance of electrical synapses/gap junctions at glutamatergic mixed synapses in the 14th spinal segment that innervates the adult male gonopodium of Western Mosquitofish, Gambusia affinis (Mosquitofish). To study gap junctions' role in fast motor behavior, we used a minimally-invasive neural-tract-tracing technique to introduce gap junction-permeant or -impermeant dyes into deep muscles controlling the gonopodium of the adult male Mosquitofish, a teleost fish that rapidly transfers (complete in <20 mS) spermatozeugmata into the female reproductive tract. Dye-coupling in the 14th spinal segment controlling the gonopodium reveals coupling between motor neurons and a commissural primary ascending interneuron (CoPA IN) and shows that the 14th segment has an extensive and elaborate dendritic arbor and more gap junctions than do other segments. Whole-mount immunohistochemistry for Cx35 results confirm dye-coupling and show it occurs via gap junctions. Finally, FRIL shows that gap junctions are at mixed synapses and reveals that >50 of the 62 gap junctions at mixed synapses are in the 14th spinal segment. Our results support and extend studies showing gap junctions at mixed synapses in spinal cord segments involved in control of genital reflexes in rodents, and they suggest a link between mixed synapses and fast motor behavior. The findings provide a basis for studies of specific roles of spinal neurons in the generation/regulation of sex-specific behavior and for studies of gap junctions' role in regulating fast motor behavior. Finally, the CoPA IN provides a novel candidate neuron for future studies of gap junctions and neural control of fast motor behaviors.
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Affiliation(s)
| | | | | | - Scott E Fraser
- Molecular and Computational Biology Section, University of Southern California Los Angeles, CA, USA
| | - Thomas Yasumura
- Department of Biomedical Sciences, Colorado State University Fort Collins, CO, USA
| | | | - John E Rash
- Department of Biomedical Sciences, Colorado State University Fort Collins, CO, USA ; Program in Molecular, Cellular and Integrative Neurosciences, Colorado State University Fort Collins, CO, USA
| | - Eduardo Rosa-Molinar
- Biological Imaging Group, University of Puerto Rico San Juan, PR, USA ; Institute of Neurobiology, School of Medicine, University of Puerto Rico San Juan, PR, USA
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Baker MW, Macagno ER. Control of neuronal morphology and connectivity: Emerging developmental roles for gap junctional proteins. FEBS Lett 2014; 588:1470-9. [DOI: 10.1016/j.febslet.2014.02.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Revised: 02/10/2014] [Accepted: 02/12/2014] [Indexed: 11/25/2022]
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Meyrand P, Bem T. Variety of alternative stable phase-locking in networks of electrically coupled relaxation oscillators. PLoS One 2014; 9:e86572. [PMID: 24520321 PMCID: PMC3919711 DOI: 10.1371/journal.pone.0086572] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Accepted: 12/12/2013] [Indexed: 11/22/2022] Open
Abstract
We studied the dynamics of a large-scale model network comprised of oscillating electrically coupled neurons. Cells are modeled as relaxation oscillators with short duty cycle, so they can be considered either as models of pacemaker cells, spiking cells with fast regenerative and slow recovery variables or firing rate models of excitatory cells with synaptic depression or cellular adaptation. It was already shown that electrically coupled relaxation oscillators exhibit not only synchrony but also anti-phase behavior if electrical coupling is weak. We show that a much wider spectrum of spatiotemporal patterns of activity can emerge in a network of electrically coupled cells as a result of switching from synchrony, produced by short external signals of different spatial profiles. The variety of patterns increases with decreasing rate of neuronal firing (or duty cycle) and with decreasing strength of electrical coupling. We study also the effect of network topology - from all-to-all – to pure ring connectivity, where only the closest neighbors are coupled. We show that the ring topology promotes anti-phase behavior as compared to all-to-all coupling. It also gives rise to a hierarchical organization of activity: during each of the main phases of a given pattern cells fire in a particular sequence determined by the local connectivity. We have analyzed the behavior of the network using geometric phase plane methods and we give heuristic explanations of our findings. Our results show that complex spatiotemporal activity patterns can emerge due to the action of stochastic or sensory stimuli in neural networks without chemical synapses, where each cell is equally coupled to others via gap junctions. This suggests that in developing nervous systems where only electrical coupling is present such a mechanism can lead to the establishment of proto-networks generating premature multiphase oscillations whereas the subsequent emergence of chemical synapses would later stabilize generated patterns.
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Affiliation(s)
- Pierre Meyrand
- Univ. Bordeaux, IMN, UMR 5293, Bordeaux, France
- CNRS, IMN, UMR 5293, Bordeaux, France
- * E-mail:
| | - Tiaza Bem
- Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland
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Yazdani N, Firme CP, Macagno ER, Baker MW. Expression of a dominant negative mutant innexin in identified neurons and glial cells reveals selective interactions among gap junctional proteins. Dev Neurobiol 2013; 73:571-86. [DOI: 10.1002/dneu.22082] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2013] [Revised: 02/25/2013] [Accepted: 02/26/2013] [Indexed: 11/12/2022]
Affiliation(s)
- Neema Yazdani
- Section of Cell and Developmental Biology; University of California; San Diego La Jolla; California; 92093
| | - Constantine P. Firme
- Section of Cell and Developmental Biology; University of California; San Diego La Jolla; California; 92093
| | - Eduardo R. Macagno
- Section of Cell and Developmental Biology; University of California; San Diego La Jolla; California; 92093
| | - Michael W. Baker
- Section of Cell and Developmental Biology; University of California; San Diego La Jolla; California; 92093
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Turner MB, Szabo-Maas TM, Poyer JC, Zoran MJ. Regulation and restoration of motoneuronal synaptic transmission during neuromuscular regeneration in the pulmonate snail Helisoma trivolvis. THE BIOLOGICAL BULLETIN 2011; 221:110-125. [PMID: 21876114 PMCID: PMC4459755 DOI: 10.1086/bblv221n1p110] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Regeneration of motor systems involves reestablishment of central control networks, reinnervation of muscle targets by motoneurons, and reconnection of neuromodulatory circuits. Still, how these processes are integrated as motor function is restored during regeneration remains ill defined. Here, we examined the mechanisms underlying motoneuronal regeneration of neuromuscular synapses related to feeding movements in the pulmonate snail Helisoma trivolvis. Neurons B19 and B110, although activated during different phases of the feeding pattern, innervate similar sets of muscles. However, the percentage of muscle fibers innervated, the efficacy of excitatory junction potentials, and the strength of muscle contractions were different for each cell's specific connections. After peripheral nerve crush, a sequence of transient electrical and chemical connections formed centrally within the buccal ganglia. Neuromuscular synapse regeneration involved a three-phase process: the emergence of spontaneous synaptic transmission (P1), the acquisition of evoked potentials of weak efficacy (P2), and the establishment of functional reinnervation (P3). Differential synaptic efficacy at muscle contacts was recapitulated in cell culture. Differences in motoneuronal presynaptic properties (i.e., quantal content) were the basis of disparate neuromuscular synapse function, suggesting a role for retrograde target influences. We propose a homeostatic model of molluscan motor system regeneration. This model has three restoration events: (1) transient central synaptogenesis during axonal outgrowth, (2) intermotoneuronal inhibitory synaptogenesis during initial neuromuscular synapse formation, and (3) target-dependent regulation of neuromuscular junction formation.
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Affiliation(s)
- M. B. Turner
- Department of Cellular Biology, University of Georgia, Athens, Georgia 30602
| | - T. M. Szabo-Maas
- Department of Biology, Brandeis University, Waltham, Massachusetts 02453
| | - J. C. Poyer
- Department of Biology, Texas A&M University, College Station, Texas 77843
| | - M. J. Zoran
- Department of Biology, Texas A&M University, College Station, Texas 77843
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Colomer C, Martin AO, Desarménien MG, Guérineau NC. Gap junction-mediated intercellular communication in the adrenal medulla: an additional ingredient of stimulus-secretion coupling regulation. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2011; 1818:1937-51. [PMID: 21839720 DOI: 10.1016/j.bbamem.2011.07.034] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2011] [Revised: 07/20/2011] [Accepted: 07/25/2011] [Indexed: 01/28/2023]
Abstract
The traditional understanding of stimulus-secretion coupling in adrenal neuroendocrine chromaffin cells states that catecholamines are released upon trans-synaptic sympathetic stimulation mediated by acetylcholine released from the splanchnic nerve terminals. Although this statement remains largely true, it deserves to be tempered. In addition to its neurogenic control, catecholamine secretion also depends on a local gap junction-mediated communication between chromaffin cells. We review here the insights gained since the first description of gap junctions in the adrenal medullary tissue. Adrenal stimulus-secretion coupling now appears far more intricate than was previously envisioned and its deciphering represents a challenge for neurobiologists engaged in the study of the regulation of neuroendocrine secretion. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
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Affiliation(s)
- Claude Colomer
- Institut de Génomique Fonctionnelle, F-34000 Montpellier, France
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Rivera-Rivera NL, Martinez-Rivera N, Torres-Vazquez I, Serrano-Velez JL, Lauder GV, Rosa-Molinar E. A male poecillid's sexually dimorphic body plan, behavior, and nervous system. Integr Comp Biol 2010; 50:1081-90. [PMID: 21082070 DOI: 10.1093/icb/icq147] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Here we review the literature of a male poecillid's sexually dimorphic body plan, behavior, and nervous system, including work dating from the mid 1800s to the mid 1990s as well as work in press or in preparation for publication. Rosa-Molinar described the remodeling of the sexually dimorphic anal fin appendicular support, confirmed earlier claims about the development of the male and female secondary sex characteristics in the Western Mosquitofish, Gambusia affinis and provided for the first time direct embryonic evidence suggesting that remodeling of the sexually dimorphic anal fin appendicular support is biphasic. The first process begins in embryos and proceeds similarly in immature males and females; the second process occurs only in males and results in the anterior transposition of the anal fin and its appendicular support to the level of vertebra 11 [Rosa-Molinar E, Hendricks SE, Rodriguez-Sierra JF, Fritzsch B. 1994. Development of the anal fin appendicular support in the western mosquitofish, Gambusia affinis (Baird and Girard, 1854): a reinvestigation and reinterpretation. Acta Anat 151:20-35.] and the formation of a gonopodium used for internal fertilization. Studies using high-speed video cameras confirmed and extended Peden's and others' observations of copulatory behavior. The cameras showed that circumduction is a complex movement combining in a very fast sequence abduction, extension and pronation, S-start-type fast-start (defined as torque-thrust), and adduction movements. Recent work on the nervous system demonstrated dye-coupling between motor neurons and interneurons via gap junctions, suggesting an attractive substrate for the rapid motions involved in poecillid copulatory reflexes.
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Affiliation(s)
- Nydia L Rivera-Rivera
- Biological Imaging Group, University of Puerto Rico-Rio Piedras, San Juan, Puerto Rico
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Szabo TM, Caplan JS, Zoran MJ. Serotonin regulates electrical coupling via modulation of extrajunctional conductance: H-current. Brain Res 2010; 1349:21-31. [PMID: 20599836 DOI: 10.1016/j.brainres.2010.06.025] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2010] [Revised: 05/03/2010] [Accepted: 06/10/2010] [Indexed: 12/30/2022]
Abstract
Synaptic strength can be highly variable from animal to animal within a species or over time within an individual. The process of synaptic plasticity induced by neuromodulatory agents might be unpredictable when the underlying circuits subject to modulation are themselves inherently variable. Serotonin (5-hydroxytryptomine; 5HT) and serotonergic signaling pathways are important regulators of animal behavior and are pharmacological targets in a wide range of neurological disorders. We have examined the effect of 5HT on electrical synapses possessing variable coupling strengths. While 5HT decreased electrical coupling at synapses with weak electrical connectivity, synapses with strong electrical coupling were less affected by 5HT treatment, as follows from the equations used for calculating coupling coefficients. The fact that the modulatory effect of 5HT on electrical connections was negatively correlated with the strength of electrical coupling suggests that the degree of electrical coupling within a neural network impacts subsequent neuromodulation of those synapses. Biophysical studies indicated that these effects were primarily due to 5HT-induced modulation of membrane currents that indirectly affect junctional coupling at synaptic contacts. In support of these experimental analyses, we created a simple model of coupled neurons to demonstrate that modulation of electrical coupling could be due solely to 5HT effects on H-channel conductance. Therefore, variability in the strength of electrical coupling in neural circuits can determine the pharmacological effect of this neuromodulatory agent.
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Affiliation(s)
- Theresa M Szabo
- Department of Biology, Brandeis University, Waltham, MA 02453, USA
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Carrascal L, Nieto-Gonzalez JL, Torres B, Nunez-Abades P. Changes in somatodendritic morphometry of rat oculomotor nucleus motoneurons during postnatal development. J Comp Neurol 2009; 514:189-202. [PMID: 19274669 DOI: 10.1002/cne.21996] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
This work investigates the somatodendritic shaping of rat oculomotor nucleus motoneurons (Mns) during postnatal development. The Mns were functionally identified in slice preparation, intracellularly injected with neurobiotin, and three-dimensionally reconstructed. Most of the Mns (approximately 85%) were multipolar and the rest (approximately 15%) bipolar. Forty multipolar Mns were studied and grouped as follows: 1-5, 6-10, 11-15, and 21-30 postnatal days. Two phases were distinguished during postnatal development (P1-P10 and P11-P30). During the first phase, there was a progressive increase in the dendritic complexity; e.g., the number of terminals per neuron increased from 26.3 (P1-P5) to 47.7 (P6-P10) and membrane somatodendritic area from 11,289.9 microm(2) (P1-P5) to 19,235.8 microm(2) (P6-P10). In addition, a few cases of tracer coupling were observed. During the second phase, dendritic elongation took place; e.g., the maximum dendritic length increased from 486.7 microm (P6-P10) to 729.5 microm in adult Mns, with a simplification of dendritic complexity to values near those for the newborn, and a slow, progressive increase in membrane area from 19,235.8 microm(2) (P6-P10) to 24,700.3 microm(2) (P21-P30), while the somatic area remained constant. In conclusion, the electrophysiological changes reported in these Mns with maturation (Carrascal et al. [2006] Neuroscience 140:1223-1237) cannot be fully explained by morphometric variations; the dendritic elongation and increase in dendritic area are features shared with other pools of Mns, whereas changes in dendritic complexity depend on each population; the first phase paralleled the establishment of vestibular circuitry and the second paralleled eyelid opening.
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Affiliation(s)
- Livia Carrascal
- Department of Physiology and Zoology, University of Seville, 41012 Seville, Spain
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