Development of Chloride-Mediated Inhibition in Neurons of the Anteroventral Cochlear Nucleus of Gerbil (Meriones unguiculatus)

2007 ◽  
Vol 98 (3) ◽  
pp. 1634-1644 ◽  
Author(s):  
Ivan Milenković ◽  
Mirko Witte ◽  
Rostislav Tureček ◽  
Marco Heinrich ◽  
Thomas Reinert ◽  
...  

At the initial stages in neuronal development, GABAergic and glycinergic neurotransmission exert depolarizing responses, assumed to be of importance for maturation, which in turn shift to hyperpolarizing in early postnatal life due to development of the chloride homeostasis system. Spherical bushy cells (SBC) of the mammalian cochlear nucleus integrate excitatory glutamatergic inputs with inhibitory (GABAergic and glycinergic) inputs to compute signals that contribute to sound localization based on interaural time differences. To provide a fundamental understanding of the properties of GABAergic neurotransmission in mammalian cochlear nucleus, we investigated the reversal potential of the GABA-evoked currents ( EGABA) by means of gramicidin-perforated-patch recordings in developing SBC. The action of GABA switches from depolarizing to hyperpolarizing by the postnatal day 7 due to the negative shift in EGABA. Furthermore, we studied the expression pattern of the K+-Cl−-extruding cotransporter KCC2, previously shown to induce a switch from neonatal Cl− efflux to the mature Cl− influx in various neuron types, thereby causing a shift from depolarizing to hyperpolarizing GABA action. The KCC2 protein is expressed in SBC already at birth, yet its activity is attained toward the end of the first postnatal week as indicated by pharmacological inhibition. Interruption of the Cl− extrusion by [(dihydroindenyl)oxy] alkanoic acid or furosemide gradually shifted EGABA in positive direction with increasing maturity, suggesting that KCC2 could be involved in maintaining low [Cl−]i after the postnatal day 7 thereby providing the hyperpolarizing Cl−-mediated inhibition in SBC.

1997 ◽  
Vol 3 (S2) ◽  
pp. 257-258
Author(s):  
S.M. Yu ◽  
C.I. Lee

Microcysts are most evident in the posteroventral and anteroventral cochlear nucleus (PVCN & AVCN) of the gerbil. They are reported as a neurodegenerative disorder or spongioform degeneration or a dynamic process related to the degree of auditory stimulation in the cochlear nucleus of the gerbil. Little information is avalable on the origin and formation of microcysts in the cochlear nucleus of the gerbil. The aim of this study was to investigate the internal morphologic changes of microcysts in the gerbil PVCN during postnatal development by scanning electron microscopy.The mongolian gerbil, Meriones unguiculatus, were sacrificed by cardiac perfusion of a saline nitrite flush, followed by a 3% glutaraldehyde in 0.1M phosphate buffer. After fixation the brain were washed in 0.1M phosphate buffer ,embedded in 5% agar, vibratome-sliced through the cochlear nucleus, and then postfixed in the 1% osmium tetroxide in 0.1M phosphate buffer for one hour. The sectioned tissues were dehydrated in a graded ethanol series to absolute ethanol and transferred to liquid carbon dioxide for critical point drying.


1997 ◽  
Vol 78 (2) ◽  
pp. 674-688 ◽  
Author(s):  
Andrei B. Belousov ◽  
Anthony N. Van Den Pol

Belousov, Andrei B. and Anthony N. van den Pol. Dopamine inhibition: enhancement of GABA activity and potassium channel activation in hypothalamic and arcuate nucleus neurons. J. Neurophysiol. 78: 674–688, 1997. Dopamine (DA) decreases activity in many hypothalamic neurons. To determine the mechanisms of DA's inhibitory effect, whole cell voltage- and current-clamp recordings were made from primary cultures of rat hypothalamic and arcuate nucleus neurons ( n = 186; 15–39 days in vitro). In normal buffer, DA (usually 10 μM; n = 23) decreased activity in 56% of current-clamped cells and enhanced activity in 22% of the neurons. In neurons tested in the presence of glutamate receptor antagonists d,l−2-amino-5-phosphonovalerate (AP5; 100 μM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 μM), DA application (10 μM) revealed heterogeneous effects on electrical activity of cells, either hyperpolarization and decrease in activity (53% of 125) or depolarization and increase in spontaneous activity (22% of 125). The DA-mediated hyperpolarization of membrane potential was associated with a decrease in the input resistance. The reversal potential for the DA-mediated hyperpolarization was −97 mV, and it shifted in a positive direction when the concentration of K+ in the incubating medium was increased, suggesting DA activation of K+ channels. Because DA did not have a significant effect on the amplitude of voltage-dependent K+ currents, activation of voltage-independent K+ currents may account for most of the hyperpolarizing actions of DA. DA-mediated hyperpolarization and depolarization of neurons were found during application of the Na+ channel blocker tetrodotoxin (1 μM). The hyperpolarization was blocked by the application of DA D2 receptor antagonist eticlopride (1–20 μM; n = 7). In the presence of AP5 and CNQX, DA (10 μM) increased (by 250%) the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) in 11 of 19 neurons and evoked IPSCs in 7 of 9 cells that had not previously shown any IPSCs. DA also increased the regularity and the amplitude (by 240%) of spontaneous IPSCs in 9 and 4 of 19 cells, respectively. Spontaneous and DA-evoked IPSCs and inhibitory postsynaptic potentials were blocked by the γ-aminobutyrate A (GABAA) antagonist bicuculline (50 μM), verifying their GABAergic origin. Pertussis toxin pretreatment (200 ng/ml; n = 15) blocked the DA-mediated hyperpolarizations, but did not prevent depolarizations ( n = 3 of 15) or increases in IPSCs ( n = 6 of 10) elicited by DA. Intracellular neurobiotin injections ( n = 21) revealed no morphological differences between cells that showed depolarizing or hyperpolarizing responses to DA. Immunolabeling neurobiotin-filled neurons that responded to DA ( n = 13) showed that GABA immunoreactive neurons ( n = 4) showed depolarizing responses to DA, whereas nonimmunoreactive neurons ( n = 9) showed both hyperpolarizing ( n = 6) and depolarizing ( n = 3) responses. DA-mediated hyperpolarization, depolarization, and increases in frequency of postsynaptic activity could be detected in embryonic hypothalamic or arcuate nucleus neurons after only 5 days in vitro, suggesting that DA could play a modulatory role in early development. These findings suggest that DA inhibition in hypothalamic and arcuate nucleus neurons is achieved in part through the direct inhibition of excitatory neurons, probably via DA D2 receptors acting through a Gi/Go protein on K+ channels, and in part through the enhancement of GABAergic neurotransmission.


PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e29965 ◽  
Author(s):  
Marei Typlt ◽  
Bernhard Englitz ◽  
Mandy Sonntag ◽  
Susanne Dehmel ◽  
Cornelia Kopp-Scheinpflug ◽  
...  

1984 ◽  
Vol 14 (2) ◽  
pp. 155-174 ◽  
Author(s):  
Robert E. Wickesberg ◽  
John W. Dickson ◽  
Mary Morton Gibson ◽  
C. Daniel Geisler

1992 ◽  
Vol 336 (1278) ◽  
pp. 403-406 ◽  

This study investigates a potential mechanism for the processing of acoustic information that is encoded in the spatiotemporal discharge patterns of auditory nerve (AN) fibres. Recent physiological evidence has demonstrated that some low-frequency cells in the anteroventral cochlear nucleus (AVCN) are sensitive to manipulations of the phase spectrum of complex sounds (Carney 1990 b ). These manipulations result in systematic changes in the spatiotemporal discharge patterns across groups of low-frequency an fibres having different characteristic frequencies (CFS). One interpretation of these results is that these neurons in the AVCN receive convergent inputs from AN fibres with different CFS, and that the cells perform a coincidence detection or cross-correlation upon their inputs. This report presents a model that was developed to test this interpretation.


2009 ◽  
Vol 102 (2) ◽  
pp. 1287-1295 ◽  
Author(s):  
Jaime G. Mancilla ◽  
Paul B. Manis

Individual neurons have been shown to exhibit target cell-specific synaptic function in several brain areas. The time course of the postsynaptic conductances (PSCs) strongly influences the dynamics of local neural networks. Cartwheel cells (CWCs) are the most numerous inhibitory interneurons in the dorsal cochlear nucleus (DCN). They are excited by parallel fiber synapses, which carry polysensory information, and in turn inhibit other CWCs and the main projection neurons of the DCN, pyramidal cells (PCs). CWCs have been implicated in “context-dependent” inhibition, producing either depolarizing (other CWCs) or hyperpolarizing (PCs) post synaptic potentials. In the present study, we used paired whole cell recordings to examine target-dependent inhibition from CWCs in neonatal rat DCN slices. We found that CWC inhibitory postsynaptic potentials (IPSPs) onto PCs are large (1.3 mV) and brief (half-width = 11.8 ms), whereas CWC IPSPs onto other CWCs are small (0.2 mV) and slow (half-width = 36.8 ms). Evoked IPSPs between CWCs exhibit paired-pulse facilitation, while CWC IPSPs onto PCs exhibit paired-pulse depression. Perforated-patch recordings showed that spontaneous IPSPs in CWCs are hyperpolarizing at rest with a mean estimated reversal potential of −67 mV. Spontaneous IPSCs were smaller and lasted longer in CWCs than in PCs, suggesting that the kinetics of the receptors are different in the two cell types. These results reveal that CWCs play a dual role in the DCN. The CWC-CWC network interactions are slow and sensitive to the average rate of CWC firing, whereas the CWC-PC network is fast and sensitive to transient changes in CWC firing.


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