Cortical Influences on Neurons of the Lateral Reticular Nucleus Responding to Noxious Stimuli

The effect of frontoparietal sensorimotor (FPSM) cortex stimulation on both the spontaneous and the noxious evoked activity of neurons in the lateral reticular nucleus (LRN) was tested in barbiturate-anesthetized rats. Ninety-three LRN neurons that responded to a noxious heat stimulus (HS) were recorded (72% antidromically fired from the cerebellum). Of these, 66 neurons altered their spontaneous firing rates in response to cortical stimulation. Two patterns of responses were found: either an excitation followed by a suppression of spontaneous activity (52 neurons), or a pure suppression of spontaneous activity lasting 50-400 msec (14 neurons). In 46 of these neurons, it was found that cortical stimulation reduced HS-evoked activity to near the baseline level. Furthermore, it was found that when applied after a prolonged cortical stimulation, the HS was ineffective. It is concluded that FPSM cortex can influence nociceptive information in LRN neurons that respond to its stimulation, possibly interfering with the mechanisms underlying stimulation-produced analgesia (SPA). In this context, it is proposed that the cortex can modulate the activity of LRN neurons that activate, through local loops, a descending antinociceptive system and also a separate projection system to the cerebellum.     

Cortical influences on neurons of the lateral reticular nucleus responding to noxious stimuli

The effect of frontoparietal sensorimotor (FPSM) cortex stimulation on both the spontaneous and the noxious evoked activity of neurons in the lateral reticular nucleus (LRN) was tested in barbiturate-anesthetized rats. Ninety-three LRN neurons that responded to a noxious heat stimulus (HS) were recorded (72% antidromically fired from the cerebellum). Of these, 66 neurons altered their spontaneous firing rates in response to cortical stimulation. Two patterns of responses were found: either an excitation followed by a suppression of spontaneous activity (52 neurons), or a pure suppression of spontaneous activity lasting 50-400 msec (14 neurons). In 46 of these neurons, it was found that cortical stimulation reduced HS-evoked activity to near the baseline level. Furthermore, it was found that when applied after a prolonged cortical stimulation, the HS was ineffective. It is concluded that FPSM cortex can influence nociceptive information in LRN neurons that respond to its stimulation, possibly interfering with the mechanisms underlying stimulation-produced analgesia (SPA). In this context, it is proposed that the cortex can modulate the activity of LRN neurons that activate, through local loops, a descending antinociceptive system and also a separate projection system to the cerebellum.     

Neurophysiological analysis of efferent-afferent interaction of neurons of the parietal associate cortex in cats

Neuronal responses of the parietal associate cortex (field 5) was recorded in waking cat during electrical stimulation of the pyramidal tract axons and afferent stimulation. The electrical stimulation of the pyramid evoked marked responses in 39% of neurons. 87% of these neurons increased spike activity during sematic nociceptive stimulation, 61% of test neurons were activated by light or tonal stimulation. Neuronal activity was recorded during defensive conditioning to the pyramidal tract axons stimulation. It has been shown that conditioned stimulation of the pyramidal tract evoked plastic changes of responses in 66% of neurons of the parietal cortex. These data are discussed relative to the possible functional role of the efferent-afferent interaction to field 5.     

Pentagastrin as a factor in the selective recruitment of dorsal hippocampal neurons in the organization of goal-directed feeding behavior

Single unit activity of the rabbit dorsal hippocamp in response to electric stimulation of the food centers of the lateral hypothalamus has been studied. Threshold stimulation produced food motivation and subthreshold one the orienting-research reactions. Microiontophoretic application to the neurons of the protein synthesis blocker cycloheximide induced changes in single unit activity in response to threshold stimulation in 79% of cases, whereas to subthreshold stimulation in 53% of cases. Application to these neurons of pentagastrin recovered the reactions only to threshold stimulation. It is inferred that the involvement of the majority of CA3 dorsal hippocampal neurons in food motivation requires the presence in the perineuronal space of a definite amount of pentagastrin that is likely to be synthesized, under normal conditions during motivational stimulation, in the given or adjacent neurons.     

Projections from the ventral subiculum to supraoptical hypothalamic region neurons not responding to stimulation of the hypophyseal pedunculus

Effects of subiculum stimulation on spike activity of neurons localized in the supraoptical nucleus (SON) and perinuclear region were studied in experiments on rats; special attention was paid to neurons that did not respond to stimulation of the hypophyseal pedunculus. With rare exception, the SON cells did not respond to subiculum stimulation; 47% of neurons in the perinuclear region were activated after subiculum stimulation, whereas in 15% the frequency of spike activity decreased. Some neurons were found in the perinuclear region that responded to subiculum stimulation by antidromic spike generation.Organization of the studied afferent input to neurons of the supraoptical region and probability of interconnections between investigated structures are discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 4, pp. 253–257, July–August, 1993.     

Effect of stimulating the medial and lateral zones of the respiratory center on the electrical activity of the diaphragm, intercostal muscles and phrenic neurons

Experiments on cats showed that the nucleus of the solitary tract displayed zones whose stimulation provoked separately stimulation or inhibition of the electrical activity of the phrenic neurons and the diaphragm. Stimulation in the nucleus ambiguus of such zones caused stimulation and inhibition of electrical activity of the intercostal inspiratory muscles. In stimulation of the corresponding zone in the giant cell nucleus the electrical activity of both groups of the inspiratory muscles proved to change. It is suggested that the action of stimulation of the giant cell nucleus zones on both groups of inspiratory muscles is mediated through the neurons of the solitary tract and the nucleus ambiguus.     

Convergence of mechanosensory inputs onto neuromodulatory serotonergic neurons in the leech

By the frequency-dependent release of serotonin, Retzius neurons in the leech modulate diverse behavioral responses of the animal. However, little is known about how their firing pattern is produced. Here we have analyzed the effects of mechanical stimulation of the skin and intracellular stimulation of mechanosensory neurons on the electrical activity of Retzius neurons. We recorded the electrical activity of neurons in ganglia attached to their corresponding skin segment by segmental nerve roots, or in isolated ganglia. Mechanosensory stimulation of the skin induced excitatory synaptic potentials (EPSPs) and action potentials in both Retzius neurons in a ganglion. The frequency and duration of responses depended on the strength and duration of the skin stimulation. Retzius cells responded after T and P cells, but before N cells, and their sustained responses correlated with the activity of P cells. Trains of five impulses at 10 Hz in every individual T, P, or N cell in isolated ganglia produced EPSPs and action potentials in Retzius neurons. Responses to T cell stimulation appeared after the first impulse. In contrast, the responses to P or N cell stimulation appeared after two or more presynaptic impulses and facilitated afterward. The polysynaptic nature of all the synaptic inputs was shown by blocking them with a high calcium/magnesium external solution. The rise time distribution of EPSPs produced by the different mechanosensory neurons suggested that several interneurons participate in this pathway. Our results suggest that sensory stimulation provides a mechanism for regulating serotonin-mediated modulation in the leech.     

The neuronal electrical responses of the superior cervical ganglion in the rabbit to nociceptive skin stimulation]

The patterns of tonic activity in the neurons of rabbit superior cervical ganglion at rest and during noxious stimulation of the skin were studied using intracellular recording. According to reflex changes in the activity patterns, all neurons studied were classified into three groups. Cardiac rhythmicity is more pronounced in the neurons of the second type than in those of the first type. The magnitude of the cardiac rhythmicity in both types of neurons was reduced after noxious stimulation of the skin. In the third type of neurons the cardiac rhythmicity was absent. In some neurons slow excitatory and inhibitory postsynaptic potentials appeared resulting from skin stimulation.     

The role of various parts of the amygdaloid complex in the regulation of activity of respiratory neurons]

In microelectrophysiological investigations influences of different nuclear regions of the amygdaloid complex on the spike activity of the functionally identified single respiratory neurons of the medulla oblongata were studied in anesthetized cats. It was established a qualitative different character of the changes of unit activity of the medullary respiratory neurons in case of stimulation of phylogenetically old corticomedial or new basolateral nuclear groups of the amygdala. It was shown higher reactivity of the investigated neurons to stimulation of the corticomedial nuclei than basolateral. The influences of the corticomedial nuclear groups on the bulbar inspiratory and expiratory neurons were facilitatory as well as inhibitory with prevailing excitatory effects. It was found that influences of the phylogenetically new neoamygdaloid structures of basolateral region on spike activity of the bulbar respiratory neurons differ accordingly to their topographical differentiation. Mechanisms of amygdaloid control of activity of the medullary respiratory neurons are discussed.     

Membrane potential synchrony in primary visual cortex during sensory stimulation

When the primary visual cortex (V1) is activated by sensory stimulation, what is the temporal correlation between the synaptic inputs to nearby neurons? This question underlies the origin of correlated activity, the mechanism of how visually evoked activity emerges and propagates in cortical circuits, and the relationship between spontaneous and evoked activity. Here, we have recorded membrane potential from pairs of V1 neurons in anesthetized cats and found that visual stimulation suppressed low-frequency membrane potential synchrony (0-10 Hz), and often increased synchrony at high frequencies (20-80 Hz). The increase in high-frequency synchrony occurred for neurons with similar orientation preferences and for neurons with different orientation preferences and occurred for a wide range of stimulus orientations. Thus, while only a subset of neurons spike in response to visual stimulation, a far larger proportion of the circuit is correlated with spiking activity through subthreshold, high-frequency synchronous activity that crosses functional domains.     

Impulse activity of the bulbar cardiovascular neurons during myocardial ischemia and stimulation of the cortical sensorimotor zone

In acute experiments on cats performed under nembutal anesthesia the stimulation of sensorimotor zone in cerebral hemisphere cortex changed the impulse activity of interneurons of bulbar cardiovascular centre and not of the afferent neurons. The analysis of the activity of afferent neurons and interneurons has shown a decrease in coordination between the reaction of these cells to the development of ischemic myocardial lesions during the cortex stimulation. In these conditions bulbar cardiovascular neurons could both increase and decrease the impulse activity. These changes seem to be the reason for the growing incidence of idioventricular ischemic arrhythmias during cortical stimulation.     

Light-addressed single-neuron stimulation in dissociated neuronal cultures with sparse expression of ChR2

Individual neurons are heterogeneous and have profound impact on population activity in a complex cortical network. Precise experimental control of the firing of multiple neurons would be therefore beneficial to advance our understanding of cell-network interactions. Except for direct intracellular stimulation, however, it is difficult to gain precise control of targeted neurons without inducing antidromic activation of untargeted neurons. To overcome this problem, we attempt to create a sparse group of photosensitized neurons via transfection of Channelrhodopsin-2 (ChR2) in primary dissociated cultures and then deliver light-addressed stimulation exclusively to these target neurons. We first show that liposome transfection was able to express ChR2 in 0.3-1.9% of cells plated depending on cell density. This spatially sparse but robust expression in our neuronal cultures offered the capability of single cell activation by illuminating a spot of light. We then demonstrated that delivering a pulsed train to photo-activate a single neuron had a substantial effect on the activity level of an entire neuronal culture. Furthermore, the activity level was controllable by altering the frequency of light illumination when 4 neurons were recruited as stimulation targets. These results suggest that organized activation of a very small population of neurons can provide better control over global activity of neuronal circuits than can single-neuron activities by themselves.     

Influences of superior laryngeal afferent stimulation on expiratory activity in cats

The effects of superior laryngeal nerve (SLN) stimulation on the activity of the expiratory muscles and medullary expiration-related (ER) neurons were investigated in 24 pentobarbital-anesthetized cats. In some experiments the animals were also paralyzed and artificially ventilated. Sustained tetanic stimulation of SLN consistently caused an apneic response associated with the appearance of tonic CO2-dependent activity in the expiratory muscles and in ER neurons located in the caudal ventral respiratory group (VRG) and the B?tzinger complex. Single shocks or brief tetani at the same stimulation intensities failed to evoke excitatory responses in the expiratory muscles and in the vast majority of ER neurons tested. At higher stimulation strengths, single shocks or short tetani elicited excitatory responses in the expiratory muscles (20- to 35-ms latency) and in the majority of ER neurons of the caudal VRG (7.5- to 15.5-ms latency). These responses were obtained only during the expiratory phase and proved to be CO2 independent. On the contrary, only inhibitory responses were evoked in the activity of B?tzinger complex neurons. The observed tonic expiratory activity most likely represents a disinhibition phenomenon due to the suppression of inspiratory activity; activation of expiratory muscles at higher stimulation intensities appears to be a polysynaptic reflex mediated by ER neurons of the caudal VRG but not by B?tzinger complex neurons.     

Septal nuclei in the regulation of vago-sensitive neurons activity of the solitary nucleus in cats

The descending influences of the septal nuclei (lateral nucleus--LSN and bed nucleus stria terminalis--BNST) on activity of viscero-sensory neurons of the nucleus of tractus solitarius (NTS) identified by stimulation of cervical part of the n. vagus were investigated in the cat anaesthetised by chloraloze-nembutal combination. It was found that out of 70 units recorded in the NTS area 50 were identified as those of primary and secondary input vagal neurons. Influence of single, paired and frequency stimulation on the septal structures was studied on these neurons. It was revealed that 30% (15 un) reacted by phase-specific response to the single stimulation of the septal nuclei. The latent period of initial excitation was in the range 5-25 ms. During the paired stimulation these neurons were not able to react to the second stimulus for the equal 10-300 ms. It was revealed that 34% (17 un) of the identified vagal neurons reacted by a tonic change of their spontaneous activity. The increase of frequency stimulation to 20 Hz evoked different changes of the rhythmical activity of the vagal neurons (increase, diminishing or inhibition). The study of interaction between central and peripheral signals in the solitary neurons induced blocking influence of descending septal discharge on the vagal test response. It is possible that the septal downward impulses reach the vago-sensitive solitary neurons indirectly through other structures of the limbic brain (amygdala, hypothalamus) and participate in modulation of the spontaneous activity of these neurons.     

Single neurone responses to tactile stimulation of the heart in the snail,Helix pomatia L.

Summary The electrical activity of the heart nerve and of single neurons in the suboesophageal ganglia were recorded during tactile stimulation of the heart. 15 neurons were identified which responded to heart stimulation by inhibiting or accelerating activity. Cells influenced by heart afferents are scattered in the visceral and in the right and left parietal ganglia.In most of the cases both decrease and increase of cell activity are caused by synaptic potentials, in some cases, however, the neuron is assumed to have a sensory character.The activity of three neurons influenced by heart stimulation was conducted into the heart nerve. These cells are central neurons of a heart-CNS-heart reflex.Some of the neurons located in the right parietal and visceral ganglia have no connection with the mechanoreceptors of the heart. Since their spikes propagate into the heart nerve, they probably take part in the extracardial regulation of heart activity.One of the neurons located in the visceral ganglion (cell V12) sends its axon into the heart nerve. The response of this neuron to heart stimulation was an increase in activity and an inhibition of the heart rate. This is an inhibitory neuron of the extracardial heart regulatory system.     

Activation of thalamic ventroposteriolateral neurons by phrenic nerve afferents in cats and rats.

It has been demonstrated that phrenic nerve afferents project to somatosensory cortex, yet the sensory pathways are still poorly understood. This study investigated the neural responses in the thalamic ventroposteriolateral (VPL) nucleus after phrenic afferent stimulation in cats and rats. Activation of VPL neurons was observed after electrical stimulation of the contralateral phrenic nerve. Direct mechanical stimulation of the diaphragm also elicited increased activity in the same VPL neurons that were activated by electrical stimulation of the phrenic nerve. Some VPL neurons responded to both phrenic afferent stimulation and shoulder probing. In rats, VPL neurons activated by inspiratory occlusion also responded to stimulation on phrenic afferents. These results demonstrate that phrenic afferents can reach the VPL thalamus under physiological conditions and support the hypothesis that the thalamic VPL nucleus functions as a relay for the conduction of proprioceptive information from the diaphragm to the contralateral somatosensory cortex.     

Activation of neurons of zone A5 of the rat brain upon hypoxic and thermonociceptive stimulation and switching off of the central respiratory generator

We recorded spike activity of noradrenergic neurons of zone A5 (n = 89) in the brain of anesthetized rats under conditions of hypoxic stimulation (breathing with pure N₂, 10 sec), thermonociceptive stimulation (tail-flick test), and reversible hypothermal blocking of the central respiratory activity. Hypoxic stimulation of peripheral O₂-sensitive chemoreceptors considerably increased the discharge frequency in all the examined neurons and induced tachypnea and a hypotensive reaction. Sixty-nine (77.5%) neurons of the studied group were tested using nociceptive stimulation (thermal stimulation of the tail); such stimulation resulted in a multifold increase in their discharge frequency. This was accompanied by tachypnea and a hypertensive response. Thus, we first demonstrated the role of nociception in the control of activity of noradrenergic neurons in zone A5 and the role of nociceptive afferent signals in the modulation of functions of the respiratory and cardiovascular systems mediated by neurons of the above zone. Under conditions of blocking of the central respiratory activity, we examined 36 (40.4%) neurons of zone A5 and first observed the effect of strong activation of a significant proportion of these cells upon switching off of respiration. This fact shows that there is an activating “respiratory” drive on neurons of zone A5 (probably, from the side of an expiratory neuronal population of the respiratory center) and allows us to hypothesize on the genesis of “respiratory” modulation of these cells. The activity of 16 (18.0%) cells was recorded under conditions of consecutive applications of the above stimuli; all the neurons were activated by the respective afferent influences. The simultaneously induced effects of hypoxic and nociceptive stimulations on the activity of neurons of zone A5 were additive. Thus, we first obtained proofs in favor of the multimodality of noradrenergic neurons of the above zone. This feature is a significant factor providing integrative interaction between the respiratory and cardiovascular systems and the system of nociception. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 305–313, July–August, 2006.     

The morphochemical characteristics and plastic restructurings of the hippocampal neurons after rhythmic stimulation of an extremity in old rabbits]

The rhythmic activity of CA1 hippocampal neurons was studied after the rhythmic (1-2 Hz) electrocutaneous forelimb stimulation (10-20 min) of 6-84-months-old rabbits. The spectral analysis of neuronal activity revealed the age-dependent decrease in ability to reproduce the rhythm of stimulation. The cytochemical data showed that the protein synthesis in the neurons under study also declined with age.     

Inhibition of nociceptive neurons by internal capsule stimulation

The mechanism of pain relief by internal capsule (IC) stimulation was investigated in 32 adult cats. Nociceptive neuronal activity of the nucleus ventralis posteromedialis (VPM), responding to contralateral pulp stimulation, was suppressed by IC stimulation to a greater extent than activity in the posterior nuclear group (PO) or centre-median nucleus. On the contrary, suppression of neuronal firing by intraventricular morphine-HCl predominated in PO neurons. These results suggest that pain relief by IC stimulation may be mediated through inhibitory effects on nociceptive neurons of the thalamic sensory relay nuclei.