Excitatory Inhibitory Neurons Research Articles

Reversible Inactivation of the Dorsal Nucleus of the Lateral Lemniscus Reveals Its Role in the Processing of Multiple Sound Sources in the Inferior Colliculus of Bats

Neurons in the inferior colliculus (IC) that are excited by one ear and inhibited by the other [excitatory-inhibitory (EI) neurons] can code interaural intensity disparities (IIDs), the cues animals use to localize high frequencies. Although EI properties are first formed in a lower nucleus and imposed on some IC cells via an excitatory projection, many other EI neurons are formed de novo in the IC. By reversibly inactivating the dorsal nucleus of the lateral lemniscus (DNLL) in Mexican free-tailed bats with kynurenic acid, we show that the EI properties of many IC cells are formed de novo via an inhibitory projection from the DNLL on the opposite side. We also show that signals excitatory to the IC evoke an inhibition in the opposite DNLL that persists for tens of milliseconds after the signal has ended. During that period, strongly suppressed EI cells in the IC are deprived of inhibition from the DNLL and respond to binaural signals as weakly inhibited or monaural cells. By relieving inhibition at the IC, we show that an initial binaural signal essentially reconfigures the circuit and thereby allows IC cells to respond to trailing binaural signals that were inhibitory when presented alone. Thus, DNLL innervation creates a property in the IC that is not possessed by lower neurons or by collicular EI neurons that are not innervated by the DNLL. That property is a change in responsiveness to binaural signals, a change dependent on the reception of an earlier sound. These features suggest that the circuitry linking the DNLL with the opposite central nucleus of the IC is important for the processing of IIDs that change over time, such as the IIDs generated by moving stimuli or by multiple sound sources that emanate from different regions of space.

NO inhibits supraoptic oxytocin and vasopressin neurons via activation of GABAergic synaptic inputs.

To study modulatory actions of nitric oxide (NO) on GABAergic synaptic activity in hypothalamic magnocellular neurons in the supraoptic nucleus (SON), in vitro and in vivo electrophysiological recordings were obtained from identified oxytocin and vasopressin neurons. Whole cell patch-clamp recordings were obtained in vitro from immunochemically identified oxytocin and vasopressin neurons. GABAergic synaptic activity was assessed in vitro by measuring GABA(A) miniature inhibitory postsynaptic currents (mIPSCs). The NO donor and precursor sodium nitroprusside (SNP) and L-arginine, respectively, increased the frequency and amplitude of GABA(A) mIPSCs in both cell types (P < or = 0.001). Retrodialysis of SNP (50 mM) onto the SON in vivo inhibited the activity of both neuronal types (P < or = 0.002), an effect that was reduced by retrodialysis of the GABA(A)-receptor antagonist bicuculline (2 mM, P < or = 0.001). Neurons activated by intravenous infusion of 2 M NaCl were still strongly inhibited by SNP. These results suggest that NO inhibition of neuronal excitability in oxytocin and vasopressin neurons involves pre- and postsynaptic potentiation of GABAergic synaptic activity in the SON.

Nitric Oxide Modulation of Supraoptic Oxytocin and Vasopressin Neurons Involves Potentiation of Gabaergic Synaptic Inputs.

P41 There is growing evidence that nitric oxide (NO) in the central nervous system functions as a local neuromodulator in water balance and osmotic regulation. However, the precise mechanisms by which these actions are mediated are still poorly understood. Neuronal nitric oxide synthase (nNOS) is abundantly expressed in the supraoptic (SON) and paraventricular (PVN) nuclei. nNOS expression is up-regulated in conditions known to stimulate oxytocin (OT) and vasopressin (VP) hormone release, such as salt loading and water deprivation. Since several studies have shown that NO mainly decreases the excitability of OT and VP neurons, NO may function as a local inhibitory feedback on activated SON neurons. In the present study we combined in vivo and in vitro electrophysiological studies to investigate whether NO-induced inhibition of SON neurons is mediated by activation of GABAergic inputs in the SON. In vivo retrodialysis of the NO-donor SNP into the SON inhibited the firing activity of both OT and VP neurons. This inhibition was largely blocked by retrodialysis of the GABA A receptor antagonist bicuculline. In order to understand the cellular mechanisms linking NO and GABAergic systems in the SON, in vitro patch clamp recordings of GABA A synaptic currents were obtained from immunochemically identified neurons in hypothalamic slices. The frequency and amplitude of miniature GABA A synaptic currents in both OT and VP neurons were significantly increased by SNP. These results suggest that NO inhibition of neuronal excitability of OT and VP neurons is largely mediated by pre- and postsynaptic potentiation of GABAergic synaptic activity in the SON. Thus, the proposed NO-GABAergic inhibitory feedback in the SON might constitute an important mechanism by which NO regulates osmotic and fluid balance homeostasis.

Noise-free stochastic resonance in simple chaotic systems

The phenomenon of stochastic resonance (SR) is reported in a completely noise-free situation, with the role of thermal noise being taken by low-dimensional chaos. A one-dimensional, piecewise linear map and a pair of coupled excitatory-inhibitory neurons are the systems used for the investigation. Both systems show a transition from symmetry-broken to symmetric chaos on varying a system parameter. In the latter state, the systems switch between the formerly disjoint attractors due to the inherent chaotic dynamics. This switching rate is found to “resonate” with the frequency of an externally applied periodic perturbation (either parametric or additive). The existence of a resonance in the response of the system is characterized in terms of the residence-time distributions. The results are an unambiguous indicator of the presence of SR-like behavior in these systems. Analytical investigations supporting the observations are also presented. The results have implications in the area of information processing in biological systems.

From GABAA receptor diversity emerges a unified vision of GABAergic inhibition.

Transmitter receptor diversity often indicates differences in transmitter receptor transduction mechanisms. This is not the case for gamma-aminobutyric acid subtype A (GABAA) receptor subtypes despite the presence of 16 genes to encode the 5 families of native GABAA receptor subtypes. Similar considerations apply to GABAC receptors and GABAB receptors. Both GABAA and GABAB receptors cause hyperpolarization of neuronal membranes and inhibition of neuronal excitability, but their mechanisms differ. GABAB receptors involve an efflux of K+ rather than an influx of Cl-, as in the case of GABAA and GABAC receptors. The stimulation of GABAA receptors can sometimes cause depolarization by Cl- efflux; this efflux is not the result of a transduction mechanism modification, but of Cl(-)-concentration gradient modification. Presumably, GABAA receptor diversity is directly linked to the inhibitory activity of basket cells and other interneuron axons, each innervating several postsynaptic neurons (cortical and hippocampal pyramidal cells for instance). Since the role of this inhibition is to entrain hippocampal and cortical pyramidal neurons into columnary activity, the GABAA receptor diversification may be a mechanism expressed by these postsynaptic neuron populations that uses different GABA potencies to synchronize pyramidal neurons into columnary activity. Thus, GABA potency variability, which emerges from GABAA receptor diversity, plays a unifying role in the intrinsic functional mechanism of laminated structures. GABAA receptor structural differences also play a role in diazepam tolerance, which is a mechanism operative in neuronal circuit adaptation to the extreme amplification of GABA-gated Cl- current intensities. Partial agonists (such as imidazenil), which modestly amplify GABA action at many GABAA receptor subtypes, fail to cause tolerance, dependence, ataxia, or ethanol and barbiturate potentiation. Partial agonists might become a new class of anxiolytic and anticonvulsant drugs that are virtually devoid of the side effects that cause serious concerns in the clinical use of full allosteric positive modulators of GABA action, such as diazepam, alprazolam, triazolam, and others. None of the above can be used as anticonvulsants because of an extremely high tolerance liability. When there is tolerance to diazepam, signs of sensitization to proconvulsive action are exhibited simultaneously. After tolerance, associated changes in GABAA recepter subtype expression are virtually reversed in 72 h. Also, 96 h after termination of long-term diazepam treatment, rats exhibit anxiety and are more sensitive to kainic acid-elicited convulsions. At the same time, these rats have an increase in brain expression of GLuR1, R2, and R3. It is believed that the supersensitivity to kainic acid, convulsions and anxiety, and the increased expression of GLuR1, R2, and R3 may be parts of the mechanism of diazepam dependence.

Characterization of responses of T2-T4 spinal cord neurons to esophageal distension in the rat.

1. Three hundred fifty neurons in the T2-T4 spinal segments of 38 intact, pentobarbital sodium-anesthetized, pancuronium-paralyzed male rats were examined for somatic receptive fields and responses to midthoracic esophageal distension (ED). Recordings were made at a depth of 0.1-1.45 mm from the dorsal spinal cord surface and from the midline to approximately 1.0 mm lateral. 2. Fifty-six of the 350 total neurons (16%) responded to ED, produced by air inflation of a latex balloon (0.5-1.5 ml). Most of these 56 neurons (84%) were excited by ED, and all except one were excited at a short latency (< 2 s) to stimulus onset. The response to ED in about one-half of all excited neurons terminated abruptly with termination of the stimulus; the other neurons exhibited an afterdischarge of 5 to > 80 s. Repeated ED at a constant intensity (1.25 ml, 30 s every 6 min) produced stable and reproducible responses of neurons excited by ED. Twenty-one percent of neurons that responded to ED were antidromically invaded from the spinomedullary junction. 3. Graded ED (0.5-1.5 ml, 30 s every 6 min) produced linear and accelerating stimulus-response functions in the 29 neurons tested. The mean threshold for distension, determined with a least-squares regression analysis, was extrapolated to near 0.5 ml of distending volume, and no difference in response threshold was found between neuronal groups with or without after-discharge. 4. The spontaneous activity of 7 of the 56 neurons (12.5%) that responded to ED was inhibited by the stimulus. Stimulus-response functions for four neurons inhibited by ED were intensity dependent. The spontaneous activity of these neurons was inhibited to a mean of 24.5% of the prestimulus control by 1.25 ml ED. 5. Two neurons of the total sample of 56 (3.5%) responded to ED (1.50 ml) in a biphasic excitatory-inhibitory manner. The excitatory component of excitatory-inhibitory neurons encoded the intensity of ED; the inhibitory component during the second half of ED was apparent only at greater distending volumes (1.25-1.5 ml). 6. Somatic receptive fields were found for 303/350 neurons, and 98% were located on the thorax and proximal forearm (all ipsilateral). Five neurons in T2-T4 spinal segments had their cutaneous receptive fields located on caudal parts of the body (tail, hindleg, scrotum).(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of juxta- and intracellular microinjection of ethanol on trigeminal motoneurons in the chronic cat

The direct cellular effects of ethanol on trigeminal motoneurons were studied in chronic cats during sleep and wakefulness. Intracellular and extracellular recordings were obtained while simultaneously injecting ethanol microdroplets onto the surface (juxtacellularly) or within the soma (intracellularly) of these motoneurons. Juxtacellular ethanol injection resulted in a suppression of neuronal excitability as well as a reduction in the amplitude of action potentials and monosynaptically-induced excitatory postsynaptic potentials. Intracellular ethanol injection led to a slight increase in excitability (i.e. membrane depolarization); concurrently, however, there was a reduction in the amplitude of spike and synaptic potentials. We conclude that the predominant response of trigeminal motoneurons to the direct application of ethanol entails a dose-dependent reduction in membrane excitability in addition to a depression of excitatory synaptic transmission. This pattern of ethanol action was observed throughout the states of quiet sleep and active sleep as well as when the animal was awake.

The effects of hydrogen ion on spinal neurons.

The effects of iontophoretically applied hydrogen ion (H+) on neuronal excitability were studied in the spinal cord of cats. The activity of extracellularly recorded neurons of the dorsal horn was either depressed or enhanced by H+ and in most cases of enhancement there was a preceding phase of depression. During intracellular recordings from motoneurons it was found that H+ application usually caused a hyperpolarization accompanied by an increase in cell input resistance. In a smaller number of cells the hyperpolarization was succeeded by a depolarization that was coupled with a decrease in input resistance. In some neurons it was shown that the depolarizing phase was more prominent and had a shorter latency when larger currents were used to eject H+. The varied reports from earlier studies of excitation or inhibition of neuronal excitability by H+ may be in part explainable by our observations that the effects may depend on the concentrations of H+ used.

Binaural response-specific bands in primary auditory cortex (AI) of the cat: Topographical organization orthogonal to isofrequency contours

The spatial distribution of neurons with different binaural response properties has been studied within the three dimensions of the primary auditory cortex (AI) in the cat. Using dichotic stimulation, 92% of neurons encountered could be classified into either the excitatory/excitatory (EE) or excitatory/inhibitory (EI) interaction class. In nearly all of almost 800 penetrations introduced along radial axes, all neurons encountered along a given penetration were of the same binaural response class. Neurons of different binaural interaction classes were spatially segregated within the plane of the cortex. Electrode penetrations made parallel to isofrequency contours traversed the mediolateral extent of AI through the middle layers of the cortex. A sharp segregation of units by binaural response class was observed in these penetrations, i.e. sequences of neurons that were all of the EE class alternated with sequences of EI neurons. The regions of uniform response to binaural stimulation formed radially organized topographical subunits that were elongated along the rostrocaudal dimension of AI. These binaural interaction bands intersect the lines of re-representation of the cochlear sensory epithelium (‘isofrequency contours’) and, thus, create subdivisions of AI that each contain a representation of the entire audible frequency domain. The implications of these results for the concept of AI as a unitary element in auditory processing are discussed.

Effects of Narcotic Analgesics on Hypothalamo-Pituitary-Thyroid Function

This chapter explores the effects of narcotic analgesics on hypothalamo-pituitary-thyroid function. The inhibitory effect of morphine on thyrotrophin (TSH) secretion is mediated via the hypothalamic-pituitary axis and probably by an excitation of inhibitory neurons that lie in the caudal hypothalamus. It appears that narcotic analgesics have a dual action on the secretion of TSH secretion; however, the predominant effect appears to be one that produces inhibition of pituitary-thyroid function. Although the mechanism(s) by which narcotic analgesics influence hypothalamicpituitary activity is not been clearly elucidated, two possibilities arise. The first is that analgesics exert their effect on the pituitary through a direct action on the hypothalamic neurosecretory cells that contain releasing factors. The second possibility focusses on the presence of the “neurotransmitters”, acetylcholine, dopamine, noradrenaline and serotonin which are found in the hypothalamus. The second possibility focusses on the presence of the “neurotransmitters”, acetylcholine, dopamine, noradrenaline and serotonin which are found in the hypothalamus.