GABA Neurotransmission of the Suprachiasmatic Nucleus Is Modified During Rat Postnatal Development

2021 ◽  
pp. 074873042110480
Author(s):  
Fernando Osuna-Lopez ◽  
Miriam E. Reyes-Mendez ◽  
J. Manuel Herrera-Zamora ◽  
Jose Luis Gongora-Alfaro ◽  
Eloy G. Moreno-Galindo ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Postnatal Development ◽  
Suprachiasmatic Nucleus ◽  
Decay Time ◽  
Circadian Variation ◽  
Gabaergic System ◽  
Gamma Aminobutyric Acid ◽  
Whole Cell Patch Clamp ◽  
Excitatory Gaba ◽  
Gaba Neurotransmission

The suprachiasmatic nucleus (SCN) of the hypothalamus is the brain structure that controls circadian rhythms in mammals. The SCN is formed by two neuroanatomical regions: the ventral and dorsal. Gamma-aminobutyric acid (GABA) neurotransmission is important for the regulation of circadian rhythms. Excitatory GABA effects have been described in both SCN regions displaying a circadian variation. Moreover, the GABAergic system transfers photic information from the ventral to the dorsal SCN. However, there is almost no knowledge about GABA neurotransmission during the prenatal or postnatal development of the SCN. Here, we used whole-cell patch-clamp recordings to study spontaneous inhibitory postsynaptic currents (IPSCs) in the two SCN regions, at two zeitgeber times (day or night), and at four postnatal (P) ages: P3-5, P7-9, P12-15, and P20-25. The results herein show that the three analyzed parameters of the IPSCs, frequency, amplitude, and decay time, were significantly affected by the postnatal age: mostly, the IPSC frequency increased with age, principally in the ventral SCN in both day and night recordings; similarly, the amplitude of IPSCs augmented with age, especially at night, whereas the IPSC decay time was reduced (it was faster) with postnatal age, mainly during the day. Our findings first reveal that parameters of GABA neurotransmission are modified by postnatal development, implying that synaptic adjustments are required for an appropriate maturation of the GABAergic system in the SCN.

scholarly journals Arginine-Vasopressin Expressing Neurons in the Murine Suprachiasmatic Nucleus Exhibit a Circadian Rhythm in Network Coherence in vivo

2021 ◽  
Author(s):  
Adam Stowie ◽  
Zhimei Qiao ◽  
Daniella Do Carmo Buonfiglio ◽  
J. Christopher Ehlen ◽  
Morris Benveniste ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Arginine Vasopressin ◽  
Single Cells ◽  
Circadian Variation ◽  
Population Level ◽  
Correlational Analysis ◽  
Constant Darkness ◽  
Peak Time

AbstractThe Suprachiasmatic Nucleus (SCN) is composed of functionally distinct sub-populations of GABAergic neurons such as vasoactive intestinal polypeptide (VIP)-, arginine vasopressin (AVP)-, gastrin releasing peptide (GRP)-, and neuromedin S (NMS)-expressing neurons which form a neural network responsible for synchronizing most physiological and behavioral circadian rhythms in mammals. To date, little is known regarding which aspects of SCN rhythmicity are generated by individual SCN neurons or neuronal sub-populations and which aspects result from neuronal interaction within a network. In this study, we address this question utilizing in vivo miniaturized microscopy to measure fluorescent GCaMP-mediated calcium dynamics in AVP neurons in the intact SCN of awake, behaving mice. This approach permits analysis of rhythms of single cells, populations, and correlational analysis among groups of AVP neurons in a field of view across the circadian and diurnal day and night. We report that AVP neurons in the murine SCN exhibit a periodic oscillatory increase in calcium of approximately 14 seconds across the day and night, in both constant darkness and under a 12:12 light-dark (LD) cycle. Using in vivo optogentically-targeted single unit activity recording, we demonstrated that these slow calcium waves are likely the result of burst-firing characteristic of AVP neurons previously reported for other brain regions. Rhythmicity analysis of several fluorescence measures suggests that individual AVP neurons exhibit unstable and stochastic rhythms, with approximately 30% of the neurons rhythmic during any given day across lighting conditions, and weak or absent rhythmicity at the population level. Network-level cross-correlational analysis revealed that coherence among neuron pairs also exhibited stochastic rhythms with about 25% of pairs rhythmic at any time. Notably, this analysis revealed a stronger rhythm at the population level than was observed in single cell analysis. The peak time of maximal coherence among AVP neuronal pairs occurs between CT/ZT 6 and 9, coinciding with the timing of maximal neuronal activity with the SCN as a whole. These results are the first to demonstrate robust circadian variation in the coordination between apparently weakly rhythmic or arrhythmic neurons suggesting that, for AVP neurons, interactions between neurons in the SCN are more influential than individual or single subpopulation activity in the regulation of mammalian circadian rhythms.

BICUCULLINE/BACLOFEN-INSENSITIVE GABA RESPONSE IN CRUSTACEAN NEURONES IN CULTURE

1994 ◽  
Vol 191 (1) ◽  
pp. 167-193
Author(s):  
C Jackel ◽  
W Krenz ◽  
F Nagy
Keyword(s):  
Reversal Potential ◽  
Membrane Conductance ◽  
Gamma Aminobutyric Acid ◽  
Action Potential Firing ◽  
Patch Clamp Technique ◽  
Conformationally Restricted ◽  
Whole Cell Patch Clamp ◽  
Gabac Receptor ◽  
Potential Firing ◽  
Sr 95531

Neurones were dissociated from thoracic ganglia of embryonic and adult lobsters and kept in primary culture. When gamma-aminobutyric acid (GABA) was applied by pressure ejection, depolarizing or hyperpolarizing responses were produced, depending on the membrane potential. They were accompanied by an increase in membrane conductance. When they were present, action potential firing was inhibited. The pharmacological profile and ionic mechanism of GABA-evoked current were investigated under voltage-clamp with the whole-cell patch-clamp technique. The reversal potential of GABA-evoked current depended on the intracellular and extracellular Cl- concentration but not on extracellular Na+ and K+. Blockade of Ca2+ channels by Mn2+ was also without effect. The GABA-evoked current was mimicked by application of the GABAA agonists muscimol and isoguvacine with an order of potency muscimol>GABA>isoguvacine. cis-4-aminocrotonic acid (CACA), a folded and conformationally restricted GABA analogue, supposed to be diagnostic for the vertebrate GABAC receptor, also induced a bicuculline-resistant chloride current, although with a potency about 10 times lower than that of GABA. The GABA-evoked current was largely blocked by picrotoxin, but was insensitive to the GABAA antagonists bicuculline, bicuculline methiodide and SR 95531 at concentrations of up to 100 µmol l-1. Diazepam and phenobarbital did not exert modulatory effects. The GABAB antagonist phaclophen did not affect the GABA-induced current, while the GABAB agonists baclophen and 3-aminopropylphosphonic acid (3-APA) never evoked any response. Our results suggest that lobster thoracic neurones in culture express a chloride-conducting GABA-receptor channel which conforms to neither the GABAA nor the GABAB types of vertebrates but shows a pharmacology close to that of the novel GABAC receptor described in the vertebrate retina.

scholarly journals Drugs of Abuse Can Entrain Circadian Rhythms

2007 ◽  
Vol 7 ◽  
pp. 203-212 ◽  
Author(s):  
Ann E. K. Kosobud ◽  
Andrea G. Gillman ◽  
Joseph K. Leffel ◽  
Norman C. Pecoraro ◽  
G. V. Rebec ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Drug Metabolism ◽  
Suprachiasmatic Nucleus ◽  
Drugs Of Abuse ◽  
Social Cues ◽  
Dark Cycle ◽  
Drug Reward ◽  
Locomotor Stimulation ◽  
Almost All

Circadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse.

Properties of spontaneous inhibitory synaptic currents in cultured rat spinal cord and medullary neurons

1996 ◽  
Vol 76 (1) ◽  
pp. 448-460 ◽  
Author(s):  
C. A. Lewis ◽  
D. S. Faber
Keyword(s):  
Spinal Cord ◽  
Time Constant ◽  
Decay Time ◽  
Cultured Cells ◽  
Decay Time Constant ◽  
Inhibitory Synapses ◽  
Gamma Aminobutyric Acid ◽  
Postsynaptic Receptor ◽  
Decay Times ◽  
Medullary Neurons

1. To identify the type(s) and properties of inhibitory postsynaptic receptor(s) involved in synaptic transmission in cultured rat embryonic spinal cord and medullary neurons, we have used whole cell patch-clamp techniques to record miniature inhibitory postsynaptic currents (mIPSCs) in the presence of tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione. 2. The mIPSCs recorded from both spinal cord and medullary neurons had skewed amplitude distributions. 3. The glycinergic antagonist strychnine and the GABAergic antagonist bicuculline each decreased both the frequency and mean peak amplitudes of mIPSCs. We conclude that both glycine and gamma-aminobutyric acid (GABA) are neurotransmitters at inhibitory synapses in our cultured cells. 4. Most (approximately 96-97%) mIPSCs decay with single-exponential time constants, and decay time distributions were consistently best fitted by the sum of four Gaussians with decay constants as follows: D1 = 5.8 +/- 0.1 (SE) ms (n = 63), D2 = 12.2 +/- 0.2 ms (n = 61), D3 = 23.2 +/- 0.4 ms (n = 54), and D4 = 44.7 +/- 1.0 ms (n = 57). We conclude that the four classes of decay times represent kinetically different inhibitory postsynaptic receptor populations. 5. Strychnine and bicuculline usually had one of two different effects on the mIPSC decay time constant distributions; either selective decreases in the frequency of mIPSCs with decay times in certain classes (i.e., the D1 class was reduced by bicuculline, the D2 class by strychnine, and the D3 and D4 classes by both antagonists) or a nonselective depression in the frequency of mIPSCs with decay times in all four classes. The particular effect observed in a given neuron was correlated with the presence or absence of ATP and guanosine 5'-triphosphate (GTP) in the patch pipette. Namely, in 71% of the antagonist applications where the pipette contained ATP and GTP, the result was a nonselective decrease in mIPSCs in all decay time constant classes. Conversely, in 54% of the antagonist applications in their absence, the result was a selective decrease in the frequency of mIPSCs in specific decay time constant classes. 6. In some experiments, mIPSCs reappeared in antagonist solution after an essentially complete block. Recovery from block in the continued presence of antagonist was never observed in the absence of ATP and GTP (8 neurons), and, at the same time, 5 of 9 neurons patched with ATP and GTP in the pipette did show recovery (56%).

Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes

1995 ◽  
Vol 268 (6) ◽  
pp. H2321-H2328 ◽  
Author(s):  
S. Zhang ◽  
T. Sawanobori ◽  
H. Adaniya ◽  
Y. Hirano ◽  
M. Hiraoka
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Decay Time ◽  
Action Potential Duration ◽  
Time Course ◽  
Ventricular Myocytes ◽  
Membrane Surface ◽  
Surface Charges ◽  
Whole Cell Patch Clamp ◽  
K Current

Effects of extracellular magnesium (Mg2+) on action potential duration (APD) and underlying membrane currents in guinea pig ventricular myocytes were studied by using the whole cell patch-clamp method. Increasing external Mg2+ concentration [Mg2+]o) from 0.5 to 3 mM produced a prolongation of APD at 90% repolarization (APD90), whereas 5 and 10 mM Mg2+ shortened it. [Mg2+]o, at 3 mM or higher, suppressed the delayed outward K+ current and the inward rectifier K+ current. Increases in [Mg2+]o depressed the peak amplitude and delayed the decay time course of the Ca2+ current (ICa), the latter effect is probably due to the decrease in Ca(2+)-induced inactivation. Thus 3 mM Mg2+ suppressed the peak ICa but increased the late ICa amplitude at the end of a 200-ms depolarization pulse, whereas 10 mM Mg2+ suppressed both components. Application of 10 mM Mg2+ shifted the voltage-dependent activation and inactivation by approximately 10 mV to more positive voltage due to screening the membrane surface charges. Application of manganese (1-5 mM) also caused dual effects on APD90, similar to those of Mg2+, and suppressed the peak ICa with slowed decay. These results suggest that the dual effects of Mg2+ on APD in guinea pig ventricular myocytes can be, at least in part, explained by its action on ICa with slowed decay time course in addition to suppressive effects on K+ currents.

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