Pre- and Postsynaptic Inhibition Mediated by GABABReceptors in Cerebellar Inhibitory Interneurons

2002 ◽  
Vol 87 (1) ◽  
pp. 183-190 ◽  
Author(s):  
Puah Mann-Metzer ◽  
Yosef Yarom
Keyword(s):  
Synaptic Transmission ◽  
Firing Rate ◽  
Molecular Layer ◽  
Outward Current ◽  
Synaptic Activity ◽  
Lower Probability ◽  
Inhibitory Interneurons ◽  
Spontaneous Firing ◽  
Synaptic Potentials ◽  
Spontaneous Firing Rate

The inhibitory interneurons in the molecular layer of the cerebellar cortex form a complex network, interconnected by both chemical and electrotonic synapses. Previous work, using voltage optical imaging in an isolated cerebellum, has indicated that these interneurons also form presynaptic inhibitory interconnections. Here we examine the participation of GABABreceptors in the proposed presynaptic inhibition by recording from the molecular layer interneurons (MLI) in cerebellar slices. The GABAB agonist, baclofen, profoundly depressed synaptic transmission; a concentration of 10 μM decreased the frequency of spontaneous inhibitory synaptic potentials by 82 ± 15% and of miniature synaptic potentials by 75 ± 13%. In simultaneous recording from two synaptically interconnected MLIs, baclofen (10 μM) increased the failure rate of synaptic transmission by a factor of 3, confirming a presynaptic mechanism, most likely mediated by a decrease in calcium conductance. A postsynaptic effect of baclofen was also found; 10 μM decreased the spontaneous firing rate by 55 ± 19% even in the presence of synaptic blockers. One hundred micromolar baclofen induced an averaged hyperpolarization of 6 ± 2 mV or an averaged 7.8 ± 3 pA net outward current that can account for the decrease in firing rate. The outward current reflects a reduction in a tonic Ca2+ current, since it was abolished by blocking Ca2+ currents and remained unchanged in the presence of Ba2+. Application of the specific GABAB blocker, CGP 55845A (1 μM), not only reversed the effects of baclofen but also increased the spontaneous firing rate and synaptic activity when applied alone. Thus in slice preparations, GABABreceptors are tonically activated by endogenous GABA. The temporal role of GABAB receptors was tested using the paired-pulse paradigm. Recording from two synaptically interconnected MLIs showed a 3.5 times lower probability of release for the second stimulus. In the isolated cerebellar preparation, a robust depression of the second inhibitory response was observed. This depression was partially blocked by CGP 55845A (2 μM). We conclude that both the pre- and postsynaptic effects of baclofen are mediated by GABAB receptors that decrease Ca2+ currents. These can serve a modulatory role as well as participating in shaping the temporal interactions between consecutive inputs.

scholarly journals The core clock genePer1phases molecular and electrical circadian rhythms in SCN neurons

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2297 ◽  
Author(s):  
Jeff R. Jones ◽  
Douglas G. McMahon
Keyword(s):  
Gene Expression ◽  
Firing Rate ◽  
Clock Gene ◽  
Biological Clock ◽  
Synaptic Activity ◽  
Spontaneous Firing ◽  
Transgenic Mouse Line ◽  
The Core ◽  
Clock Gene Expression ◽  
Spontaneous Firing Rate

The brain’s biological clock, the suprachiasmatic nucleus (SCN), exhibits endogenous 24-hour rhythms in gene expression and spontaneous firing rate; however, the functional relationship between these neuronal rhythms is not fully understood. Here, we used aPer1::GFP transgenic mouse line that allows for the simultaneous quantification of molecular clock state and firing rate in SCN neurons to examine the relationship between these key components of the circadian clock. We find that there is a stable, phased relationship between E-box-driven clock gene expression and spontaneous firing rate in SCN neurons and that these relationships are independent of light input onto the system or of GABAAreceptor-mediated synaptic activity. Importantly, the concordant phasing of gene and neural rhythms is disrupted in the absence of the homologous clock genePer1, but persists in the absence of the core clock genePer2. These results suggest thatPer1plays a unique, non-redundant role in phasing gene expression and firing rate rhythms in SCN neurons to increase the robustness of cellular timekeeping.

Spontaneous firing rate of neurones in the prefrontal cortex of the rat: evidence for a dopaminergic inhibition

1976 ◽  
Vol 116 (3) ◽  
pp. 516-522 ◽  
Author(s):  
F. Mora ◽  
K.F. Sweeney ◽  
E.T. Rolls ◽  
A.M. Sanguinetti
Keyword(s):  
Prefrontal Cortex ◽  
Firing Rate ◽  
Spontaneous Firing ◽  
Spontaneous Firing Rate

Neurodepressing Hormone (Ndh): Fact or Fiction?

Crustaceana ◽  
1996 ◽  
Vol 69 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Alberto Huberman
Keyword(s):  
Molecular Weight ◽  
Firing Rate ◽  
Low Molecular Weight ◽  
Spontaneous Firing ◽  
Sinus Gland ◽  
Spontaneous Firing Rate

AbstractExtracts of the crustacean eyestalk, and particularly of the sinus gland, produce an inhibition of the spontaneous firing rate of motor and sensitive neurons in two different bioassays. This activity can be ascribed to a molecule of low molecular weight, neutral, non-peptidic, soluble in water and methanol, thermostable, different from GABA but suppressed by picrotoxin. Its nature remains to be elucidated.

scholarly journals Regulation of Neuronal Function by Choline and 4OH-GTS-21 Through α7 Nicotinic Receptors

2003 ◽  
Vol 89 (4) ◽  
pp. 1797-1806 ◽  
Author(s):  
Vladimir V. Uteshev ◽  
Edwin M. Meyer ◽  
Roger L. Papke
Keyword(s):  
Firing Rate ◽  
Direct Action ◽  
Choline Uptake ◽  
Spontaneous Firing ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Physiological Concentration ◽  
Α7 Nachr ◽  
Synaptic Functions ◽  
Neuronal Functions ◽  
Spontaneous Firing Rate

A unique feature of α7 nicotinic acetylcholine receptor physiology is that, under normal physiological conditions, α7 receptors are constantly perfused with their natural selective agonist, choline. Studying neurons of hypothalamic tuberomammillary (TM) nucleus, we show that choline and the selective α7 receptor agonist 4OH-GTS-21 can regulate neuronal functions directly, via activation of the native α7 receptors, and indirectly, via desensitizing those receptors or transferring them into a state “primed” for desensitization. The direct action produces depolarization and thereby increases the TM neuron spontaneous firing (SF) rate. The regulation of the spontaneous firing rate is robust in a nonphysiological range of choline concentrations >200 μM. However, modest effects persist at concentrations of choline that are likely to be attained perineuronally under some conditions (20–100 μM). At high physiological concentration levels, the indirect choline action reduces or even eliminates the responsiveness of α7 receptors and their availability to other strong cholinergic inputs. Similarly to choline, 4OH-GTS-21 increases the TM neuron spontaneous firing rate via activation of α7 receptors, and this regulation is robust in the range of clinically relevant concentrations of 4OH-GTS-21. We conclude that factors that regulate choline accumulation in the brain and in experimental slices such as choline uptake, hydrolysis of ACh, membrane phosphatidylcholine catabolism, and solution perfusion rate influence α7 nAChR neuronal and synaptic functions, especially under pathological conditions such as stroke, seizures, Alzheimer's disease, and head trauma, when the choline concentration in the CSF is expected to rise.

Spontaneous firing in primary afferent neurons of ampullary electroreceptor organs as attribute of bandwidth, threshold, and topology

2008 ◽  
Vol 58 (3) ◽  
pp. 301-312
Author(s):  
Franklin Bretschneider ◽  
Robert Peters ◽  
Lonneke Eeuwes
Keyword(s):  
Firing Rate ◽  
Carrier Frequency ◽  
Signal To Noise Ratio ◽  
Phase Locking ◽  
Spontaneous Firing ◽  
Sensory Stimuli ◽  
Firing Rates ◽  
Coefficients Of Variation ◽  
Electrical Stimuli ◽  
Spontaneous Firing Rate

AbstractSpontaneous firing of neurons plays an essential part in the detection of sensory stimuli. Spontaneous firing of primary afferents of ampullary electroreceptor organs in the catfish Ameiurus nebulosus (Lesueur, 1819) was studied in relation to the distribution, thresholds, and frequency characteristics of the electroreceptor organs. The spontaneous firing rate was correlated with the place on the skin. The mean inter-spike interval in 55 dorsal and 49 ventral ampullary organs in five specimens was 16.8 ms +/- 0.41 SEM and 20.5 ms +/- 0.48 SEM, corresponding to firing rates of 59.5 and 48.7 s-1 respectively. The concomitant coefficients of variation were 0.33 and 0.29. Approximately half of the dorsal ampullae were innervated by two fibres. The firing rates of each of the two fibres was lower than the firing rate of organs innervated by a single neuron. Responses to stimuli as weak as 10 pA could be recovered from the noisy average firing level provided the number of averaging sweeps was sufficiently large. This was equivalent to a stimulus of 0.025 μV/cm and was lower than the behavioural threshold of 1 μV/cm. The gain of the frequency response was enhanced at the carrier frequency, at twice the carrier frequency, and in the range from 75-90 Hz. The results revealed that the occurrence of spontaneous activity improved the signal to noise ratio of responses to electrical stimuli by reduction of the coefficient of variation, absence of a threshold, and phase locking.

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