Reaction of neurons of the medial geniculate body to acoustic stimulation

Responses of medial geniculate body (MGB) neurons to pure tones and clicks were studied in acute experiments in immobilized cats, preliminary operations being performed under calypsol anaesthesia. MGB units were identified by their reactions to cortical zone AI and brachium of inferior colliculus stimulations. When tonal stimuli were applied relay neurons of pars principalis of MGB usually demonstrated either unimodal tuning curves with narrow frequency band or fragmental ones with several narrow bands. On-response with subsequent inhibition of the background activity or without such an inhibitory period was most frequent type of the reaction (66.6%) of relay MGB neurons to tonal stimulation. The group of relay neurons with the tonic type of reaction (9.1%) was classified for which the duration of tonic response depends on the duration of tonal stimulus. Change of the excitatory reaction to the inhibitory one when the characteristic tone frequency is changed by non-characteristic++ ones is supposed to be a mechanism supplying sharpness of tuning at relay MGB neurons. It is concluded that responses of acoustic cortical neurons to sound stimulation depend to a great extent on the pattern of impulsation that comes from MGB relay units.     

Potentiation of glutamatergic synaptic input to supraoptic neurons by presynaptic nicotinic receptors

The release of vasopressin and oxytocin from the supraoptic nucleus (SON) neurons is tonically regulated by excitatory glutamatergic and inhibitory GABAergic synaptic inputs. Acetylcholine is known to excite SON neurons and to elicit vasopressin release. Cholinergic receptors are located pre- and postsynaptically in the SON, but their functional significance in the regulation of SON neurons is not fully understood. In this study, we determined the role of presynaptic cholinergic receptors in regulation of the excitatory glutamatergic inputs to the SON neurons. The magnocellular neurons in the rat hypothalamic slices were identified microscopically, and the spontaneous miniature excitatory postsynaptic currents (mEPSCs) were recorded using the whole cell voltage-clamp technique. The mEPSCs were abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM). Acetylcholine (100 microM) significantly increased the frequency of mEPSCs of 38 SON neurons from 1.87 +/- 0.36 to 3.42 +/- 0.54 Hz but did not alter the amplitude (from 19.61 +/- 0.90 to 19.34 +/- 0.84 pA) and the decay time constant of mEPSCs. Furthermore, the nicotinic receptor antagonist mecamylamine (10 microM, n = 16), but not the muscarinic receptor antagonist atropine (100 microM, n = 12), abolished the excitatory effect of acetylcholine on the frequency of mEPSCs. These data provide new information that the excitatory effect of acetylcholine on the SON neurons is mediated, at least in part, by its effect on presynaptic glutamate release. Activation of presynaptic nicotinic, but not muscarinic, receptors located in the glutamatergic terminals increases the excitatory synaptic input to the SON neurons of the hypothalamus.     

ACh受体在皮质酮引起的大鼠延髓腹外侧区前交感神经元反应中的作用

目的：研究乙酰胆碱（ACh)受体在皮质酮（CORT）对大鼠头端延髓腹外侧区（RVLM）前交感神经元快速效应中的作用,探讨糖皮质激素在交感心血管活动调节中的非基因组机制。方法：本研究采用细胞外记录和微电泳等方法观察CORT对氨基甲酸乙酯麻醉大鼠RVLM前交感神经元的作用,观察分别给予ACh受体拮抗剂阿托品（ATR）、筒箭毒（d-TC)或六烃季铵（C6）后CORT对RVLM前交感神经元的影响。结果：在RVLM共记录到33个前交感神经元,CORT能导致25（76％）个前交感神经元快速兴奋,且具有剂量依赖性,余8个前交感神经元没有反应;其中被CORT兴奋的10个单位微电泳ART后神经元的放电明显下降,但对CORT导致的兴奋作用没有明显的影响。分别向7和6个被CORT兴奋的前交感神经元微电泳d-TC和C6后,单位放电没有变化,同时对CORT导致的兴奋作用无影响。结论：CORT对RVLM前交感神经元具有快速的兴奋作用,这种作用可能并不通过ACh受体介导。     

Hexamethonium, nicotinic receptor blocker, changes the neuronal reactions on glutamate in the medial septal area in vitro

Despite the great interest in studying the medial septal area, the interactions of its neurochemical systems are not yet clearly understood. The aim of this study was to elucidate the role of nicotinic receptors in the interaction of glutamatergic and cholinergic systems of the medial septal area. The effect of L-glutamate (1 microM) on septal neurons was studied under the application of hexamethonium, nicotinic cholinoreceptor blocker by using the method of extracellular recording of neuronal activity in brain slices of ground squirrels. The response of septal neurons to glutamate depended on the type of their initial activity and on the presence of pacemaker properties. For the first time, the ability of septal neurons to respond to glutamate with an increase in burst frequency was shown. The influence of hexamethonium on the neuronal activity was similar to that of glutamate. After a preliminary application of hexamethonium, the reactions of neurons to glutamate changed. The excitatory reactions were masked, while the inhibitory reactions became stronger. It was found that nicotinic cholinergic receptors modulated the reactions of MS-DB cells to glutamate and the expression of the oscillatory properties of the septal neuronal network.     

Close encounters: how cortical neurons find and connect to their correct synaptic partners depends on the cell type

In this issue of Neuron, Stepanyants et al. embark on quantitative analyses of the axonal and dendritic arbors of cortical neurons. They test whether the paths taken by axons actually bring them closer to their true synaptic partners than they would have gotten by chance encounters based on the same axon trajectories. The results depend on the type of presynaptic neuron. Inhibitory cells take paths that explicitly link them to their actual partners while excitatory axons are as likely to have close encounters with actual partners as with other neurons. These results suggest that the mechanisms for selectivity depend on the type of presynaptic neuron.     

The unfolded protein response regulates glutamate receptor export from the endoplasmic reticulum

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors mediate the majority of excitatory signaling in the CNS, and the functional properties and subcellular fate of these receptors depend on receptor subunit composition. Subunit assembly is thought to occur in the endoplasmic reticulum (ER), although we are just beginning to understand the underlying mechanism. Here we examine the trafficking of Caenorhabditis elegans glutamate receptors through the ER. Our data indicate that neurons require signaling by the unfolded protein response (UPR) to move GLR-1, GLR-2, and GLR-5 subunits out of the ER and through the secretory pathway. In contrast, other neuronal transmembrane proteins do not require UPR signaling for ER exit. The requirement for the UPR pathway is cell type and age dependent: impairment for receptor trafficking increases as animals age and does not occur in all neurons. Expression of XBP-1, a component of the UPR pathway, is elevated in neurons during development. Our results suggest that UPR signaling is a critical step in neural function that is needed for glutamate receptor assembly and secretion.     

Attentional modulation of firing rate and synchrony in a model cortical network

The response of a neuron in the visual cortex to stimuli of different contrast placed in its receptive field is commonly characterized using the contrast response curve. When attention is directed into the receptive field of a V4 neuron, its contrast response curve is shifted to lower contrast values (Reynolds et al., 2000). The neuron will thus be able to respond to weaker stimuli than it responded to without attention. Attention also increases the coherence between neurons responding to the same stimulus (Fries et al., 2001). We studied how the firing rate and synchrony of a densely interconnected cortical network varied with contrast and how they were modulated by attention. The changes in contrast and attention were modeled as changes in driving current to the network neurons. We found that an increased driving current to the excitatory neurons increased the overall firing rate of the network, whereas variation of the driving current to inhibitory neurons modulated the synchrony of the network. We explain the synchrony modulation in terms of a locking phenomenon during which the ratio of excitatory to inhibitory firing rates is approximately constant for a range of driving current values. We explored the hypothesis that contrast is represented primarily as a drive to the excitatory neurons, whereas attention corresponds to a reduction in driving current to the inhibitory neurons. Using this hypothesis, the model reproduces the following experimental observations: (1) the firing rate of the excitatory neurons increases with contrast; (2) for high contrast stimuli, the firing rate saturates and the network synchronizes; (3) attention shifts the contrast response curve to lower contrast values; (4) attention leads to stronger synchronization that starts at a lower value of the contrast compared with the attend-away condition. In addition, it predicts that attention increases the delay between the inhibitory and excitatory synchronous volleys produced by the network, allowing the stimulus to recruit more downstream neurons. Action Editor: David Golomb     

NMDA-dependent and NMDA-independent neuronal processes in the cat motor cortex,disinhibited by bicuculline,during forepaw placement conditioning

Neuronal activity associated with a conditioned forepaw placing reaction was recorded in the cat's motor cortex locally disinhibited by bicuculline spontaneously diffused from the recording pipette. Electrical stimulation of the parieral cortex (area 5) with 3-5 pulses was used as a conditioned stimulus. In both naive and trained cats, adding of APV (NMDA receptor blocker) led to disappearance of the late (30-120 ms) secondary excitatory responses from the pattern of the neuronal reaction to the parietal stimulation recorded in the motor cortex. At the same time, the APV administration did not change the excitatory reactions (recorded, predominantly, in the deep cortical layers) time-locked to the execution of the conditioned movement. The conditioning resulted in a statistically significant increase in the amplitude and duration of the late secondary responses as well as in a shortening of their latency. In some cases (after a long period of training), the late secondary responses to the conditioned stimulus transformed into paroxysmal epileptiform bursts. A hypothesis is discussed that the increase in synaptic strength of the backward horizontal collaterals of layer-II/III pyramidal neurons is responsible for the learning-related changes in the neuronal reactions in the disinhibited motor cortex.     

Analysis of stability of neural network with inhibitory neurons

Phase coding in a neural network composed of neural oscillators with inhibitory neurons was studied based on the theory of stochastic phase dynamics. We found that with increasing the coupling coefficients of inhibitory neural oscillators, the firing density in excitatory population transits to a critical state. In this case, when we increase the inhibitory coupling, the firing density will come into dynamic balance again and tend to a fixed value gradually. According to the phenomenon, in the paper we found parameter regions to exhibit those different population states, called dividing zones including flat fading zone, rapid fading zone and critical zone. Based on the dividing zones we can choose the number ratio between inhibitory neurons and excitatory neurons in the neural network, and estimate the coupling action of inhibitory population and excitatory population. Our research also shows that the balance value, enabling the firing density to reach the dynamic balance, does not depend on initial conditions. In addition, the critical value in critical state is only related to the number ratio between inhibitory neurons and excitatory neurons, but is independent of inhibitory coupling and excitatory coupling.     

TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na⁺-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of l-glutamate.     

Responses of auditory cortex neurons in unanesthetized cats to best-frequency tones

The characteristics of extra- and intracellular responses of neurons in the AI region were studied in experiments with unanesthetized cats. It was established that auditory cortex neurons with similar best frequencies showed different forms of responses to tones of the corresponding frequency. About 40% of the auditory cortex neurons generated on responses to tone presentation. On — off and off responses were found in 27% of the neurons. Cortical neurons (27%) in which stimulation or inhibition of impulse discharge persisted throughout tone action were assigned to the tonic type group of cells. Approximately 6% of neurons in the AI region did not respond to a tone. During intracellular recording about 85% of the neurons responded to the turning on and/or off of a tone by generating an action potential followed by an IPSI. In 96% of the cortical neurons studied the IPSPs were a constant component of the intracellular responses to a tone. It is concluded that the inhibition of the impulse activity of the given neurons is of primarily a postsynaptic origin. Neurons showing one or another form of response differ from one another in the relative intensity and time characteristics of excitatory and inhibitory processes interacting on their postsynaptic membranes. In neurons of the phasic type inhibitory processes are dominant over excitatory, while excitatory processes are predominant in neurons of the tonic type.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 500–508, July–August, 1985.     

Some receptor properties in motor neurons of an Aplysia withdrawal reflex.

Glutamate or a glutamate-related substance is the neurotransmitter used at the majority of the excitatory junctions of the neuronal network mediating the gill and siphon withdrawal reflex in Aplysia. In this report, we have studied some receptor properties of the major postsynaptic elements of the network, the motor neurons. We have examined the effect of a compound interfering with glutamate receptor, concanavalin A (con A). We found that con A treatment transforms the mainly hyperpolarizing responses to L-glutamate in motor neurons to prolonged depolarizing ones; these latter responses are sensitive to CNQX. We have also examined whether con A could enhance the CNQX sensitive excitatory postsynaptic potentials in these motor neurons. We found, by contrast, that con A did not alter the synaptic responses. The possible implications of the differential effect of con A on the glutamate responses and the synaptic responses are discussed.     

The modulation of the pulse activity of neocortical neurons during a conditioned reflex]

Spontaneous and evoked activity of neurons in the sensorimotor cortex was recorded in cats with learned conditioned placing reaction before, during, and after the iontophoretic application of synaptically active substances. It was shown that apart from direct excitatory effect on the cortical neurons during its application, glutamate (Glu) exerted some modulatory influence on unit activity in subsequent 20 min. Noradrenaline suppressed the background and evoked activity through beta 1 adrenoreceptors. Activation of beta 2 adrenoreceptors by metaproterenol was accompanied by facilitation of the background and evoked activity during application and 10-20 min after. The joint application of Glu and metaproterenol improved facilitation of neuronal responses evoked by conditioned stimuli. Application of levodopa, like Glu, increased the background and evoked activity of many sensorimotor cortical neurons. The joint effect of Glu and levodopa was not substantially more intensive than the changes produced by the isolated application of any of these substances. A nonselective blocker of DA1 and DA2 receptors haloperidol either increased or did not change the background and evoked activity of some cortical neurons. In contrast to isolated application of Glu, simultaneous application of Glu and haloperidol to neocortex suppressed the neuronal responses associated with conditioned movements. The results suggest that the Glu-induced potentiation is substantially realized through molecular mechanisms common for Glu and dopamine, probably, through Gi-proteins. The conclusion is drawn that the adrenergic and dopaminergic inputs to neocortical neurons are involved in the Glu-mediated plastic changes in the cortex during conditioning.     

Dependence of responses of central auditory neurons on the depth and rate of frequency modulation

Unit responses of the inferior colliculi of anesthetized albino rats to frequency-modulated stimuli were studied. The number of spikes and the pattern and duration of the unit discharges in response to frequency modulation in different directions were shown to depend on the depth and rate of modulation. With a change in the rate of frequency modulation the number of spikes in the discharge of individual neurons could increase, decrease, or remain constant. Neurons of the inferior colliculi give their material discharge at different rates of frequency modulation. A change in the depth and rate of modulation did not change the sensitivity of most neurons to the direction of the frequency change in the stimulus within the frequency range corresponding to the center of the excitatory zone of the unit response.     

A major role for intracortical circuits in the strength and tuning of odor-evoked excitation in olfactory cortex

In primary sensory cortices, there are two main sources of excitation: afferent sensory input relayed from the periphery and recurrent intracortical input. Untangling the functional roles of these two excitatory pathways is fundamental for understanding how cortical neurons process sensory stimuli. Odor representations in the primary olfactory (piriform) cortex depend on excitatory sensory afferents from the olfactory bulb. However, piriform cortex pyramidal cells also receive dense intracortical excitatory connections, and the relative contribution of these two pathways to odor responses is unclear. Using a combination of in vivo whole-cell voltage-clamp recording and selective synaptic silencing, we show that the recruitment of intracortical input, rather than olfactory bulb input, largely determines the strength of odor-evoked excitatory synaptic transmission in rat piriform cortical neurons. Furthermore, we find that intracortical synapses dominate odor-evoked excitatory transmission in broadly tuned neurons, whereas bulbar synapses dominate excitatory synaptic responses in more narrowly tuned neurons.     

Neuroligin-1 Overexpression in Newborn Granule Cells In Vivo

Adult-born dentate granule cells integrate into the hippocampal network, extend neurites and form synapses in otherwise mature tissue. Excitatory and inhibitory inputs innervate these new granule cells in a stereotyped, temporally segregated manner, which presents a unique opportunity to study synapse development in the adult brain. To examine the role of neuroligins as synapse-inducing molecules in vivo, we infected dividing neural precursors in adult mice with a retroviral construct that increased neuroligin-1 levels during granule cell differentiation. By 21 days post-mitosis, exogenous neuroligin-1 was expressed at the tips of dendritic spines and increased the number of dendritic spines. Neuroligin-1-overexpressing cells showed a selective increase in functional excitatory synapses and connection multiplicity by single afferent fibers, as well as an increase in the synaptic AMPA/NMDA receptor ratio. In contrast to its synapse-inducing ability in vitro, neuroligin-1 overexpression did not induce precocious synapse formation in adult-born neurons. However, the dendrites of neuroligin-1-overexpressing cells did have more thin protrusions during an early period of dendritic outgrowth, suggesting enhanced filopodium formation or stabilization. Our results indicate that neuroligin-1 expression selectively increases the degree, but not the onset, of excitatory synapse formation in adult-born neurons.     

Effect of motilin on the discharge of rat hippocampal neurons responding to gastric distension and its potential mechanism

The study aims to find the effect of motilin on neuronal activity of gastric distension-responsive neurons in rat hippocampus and its possible mechanism. Single unit discharges in the hippocampal CA1 region were recorded extracellularly by means of four-barrel glass micropipettes in anesthetized rats and the expression of nNOS in hippocampus was observed by fluo-immunohistochemistry staining. Of the 171 recorded neurons, 76.0% were GD-excitatory (GD-E) neurons and 24.0% were GD-inhibited (GD-I) neurons. The 57.6% of GD-E neurons showed an excitatory response to motilin and the same effect was observed in 51.7% GD-I neurons. However, when NOS inhibitor nitro-l-arginine methyl ester (l-NAME) was administrated previously, the followed motilin-induced excitatory responsiveness of GD-responsive neurons was reduced. In contrast, discharge activity of GD-responsive neurons with motilin was enhanced by pretreatment of NO precursor l-arginine. The expression of nNOS-IR positive neurons was significantly increased in CA1 after administration of motilin. Our findings suggested that motilin excited the GD-responsive neurons in the hippocampal CA1 region and the excitatory effect of motilin may be mediated by the endogenous NO.     

Neuronal mechanisms of defense reaction to statocyst receptor stimulation in the freshwater snail Planorbarius corneus

Tilting of the freshwater snailPlanorbarius corneus triggering dynamic statocyst receptor response resulted in defense reaction attended by rapid lowering of the shell over the head, foreshortening of the foot, and inhibited locomotion and buccal apparatus operation. Large numbers of neurons from different ganglia were found to take part in this reaction in isolated nervous system preparations. The response usually followed an "all or none" pattern and did not depend on which statocyst receptors had been stimulated. Each successive response arose no sooner than 10–20 sec after the previous reaction to tilting the preparation. It is deduced that defense reaction to statocyst receptor stimulation takes the form of a "fixed action" governed by a special central mechanism. It was found during the process of investigating interaction between response to statocyte receptor and cutaneous nerve stimulation that the same central mechanism serves to produce defense reactions evoked by presentation of different stimuli.     

Effect of the opiate antagonist naloxone on the electrical activity of identified neurons in the edible snail

The opiate antagonist naloxone modifies the electric activity of some identified neurons of the Helix lucorum which have not been preliminary exposed to the effect of exogenous opioids. Some neurons are excited while others are inhibited by naloxone, and in both cases the reaction may have both a short and long latent period. The reactions depend on naloxone dose and become less expressed or are blocked when naloxone is administered together with the agonists of opiate receptor (morphine, D-Ala2, D-Leu5-enkephalin, bremazocine and beta-endorphin). Opioids alone do not produce any effect on neurons. The effect of naloxone on neurons is assumed to be a result of the elimination by the opiate antagonist of the tonic effect of endogenous opioids by their replacing on opiate receptors which are constantly stimulated by endogenous ligands.     

The Kv4.2 mediates excitatory activity-dependent regulation of neuronal excitability in rat cortical neurons

Neuronal excitability can cooperate with synaptic transmission to control the information storage. This regulation of neuronal plasticity can be affected by alterations in neuronal inputs and accomplished by modulation of voltage-dependent ion channels. In this study, we report that enhanced excitatory input negatively regulated neuronal excitability. Enhanced excitatory input by glutamate, electric field stimulation or high K⁺ increased transient outward K⁺ current, whereas did not affect the delayed rectifier K⁺ current in rat cultured cortical neurons. Both the voltage-dependent K⁺ channel 4.2 and 4.3 subunits contributed to the increase. The increase in the K⁺ current density by Kv4.2 was ascribed to its cytoplasmic membrane translocation, which was mediated by NMDA type of glutamate receptor. Furthermore, enhanced excitatory input inhibited neuronal excitability. Taken together, our results suggest that excitatory neurotransmission affects neuronal excitability via the regulation of the K⁺ channel membrane translocation.