Selective synaptic antagonism by atropine and alpha-aminoadipate of pulvinar and cortical afferents to the suprasylvian visual area (Clare-Bishop area)

The synaptic excitations of cells of the Clare-Bishop cortical region produced by electrical stimulation of the pulvinar and ipsilateral cortex, have been shown to be differentially antagonized by iontophoretically applied antagonists. Atropine attenuated the responses evoked by pulvinar stimulation without having an appreciable effect against either iontophoretically applied aspartate or cortically evoked responses. alpha-Aminoadipate antagonized aspartate elicited excitations and those obtained with cortical stimulation while leaving unaffected acetylcholine and pulvinar evoked responses. The results are supportive of the view that acetylcholine and aspartate, or a similar excitatory amino acid, act as synaptic transmitters of some afferents from the pulvinar and ipsilateral cerebral cortex, respectively.     

Cortex mapping of ipsilateral somatosensory area following anatomical hemispherectomy: A MEG study

A remarkable preservation of sensorimotor function is observed in patients with refractory epilepsy who were treated by hemispherectomy. Cortical regions in the remaining hemisphere or contralateral subcortical region contribute to the residual sensorimotor function. Somatosensory evoked field (SEF) is used to investigate the residual sensory function in hemispherectomized patients. The SEFs are usually recorded with magnetoencephalography (MEG). The objective is to investigate the ipsilateral cortical regions associated with residual sensory function in hemispherectomized patients using somatosensory evoked field techniques. Six patients with anatomical hemispherectomy were included. Ipsilateral and contralateral sensory functions were assessed by physical examination. Somatosensory evoked fields to electrical stimulation of the bilateral median nerves were recorded by MEG in the hemispherectomized patients and six control subjects. The stimulus intensity was adjusted to the minimum threshold that elicited a thumb twitch. The presumed neuronal source was identified as the equivalent current dipole. Six patients demonstrated different degrees of residual sensory function. Three patients had somatosensory evoked field activation in the ipsilateral cortex upon electrical stimulation of the hemiplegic hand. In these patients the locations of the ipsilateral sensorimotor cortex activation were in the primary somatosensory cortex (SI). The latency of the reliable somatosensory evoked field after stimulation of the median nerve was significantly longer for responses from the hemiplegic side compared with responses to stimulation of the median nerve from the normal side. In conclusion, ipsilateral sensory function has a time-locked relation to the cortical electromagnetic activation in the SI area of hemispherectomized patients.     

The effects of acetylcholine and of synaptic stimulation on the sensorimotor cortex of cats. I. Neuronal responses to stimulation of the reticular formation

This study looks into the relationship between the effects of acetylcholine on single neurons in the sensorimotor cortex of cats and the synaptic transmission of impulses to these neurons from the mesencephalic reticular formation. The effects of general anesthesia on the neuronal responses to drugs and to synaptic stimulation were avoided by using ence´phale isole´preparations; because the neuronal firing in these preparations fluctuates as it does in normal cats, long periods of recording were obtained and analyzed by the computation of histograms of the distribution of action potentials.The iontophoretic application of acetylcholine from extracellular multibarreled micropipettes increased the firing rate of about one-third of 103 neurons studied and decreased it in about one-sixth of them. Repetitive electrical stimulation of the reticular formation produced unsustained, multiphasic, or sustained changes of firing in many neurons; initial excitation was more common than initial depression. Many neurons reacted by excitation to both acetylcholine and reticular stimulation, but some neurons were depressed by acetylcholine and excited by reticular stimulation, while others were excited by acetylcholine and depressed by reticular stimulation, and still other neurons were depressed by both agents. Atropine and scopolamine, which antagonized the effects of acetylcholine, also blocked the excitatory responses to reticular stimulation in some acetylcholine-excited neurons. However, the depressant effects of reticular stimulation were not antagonized by these agents.These results support the assumption that acetylcholine acts as a synaptic transmitter of the excitatory responses to reticular stimulation in some of the neurons in the sensorimotor cortex.     

Postsynaptic potentials evoked in spiny neostriatal projection neurons by stimulation of ipsilateral and contralateral neocortex

Postsynaptic potentials were evoked in neostriatal neurons by stimulation of the ipsilateral and contralateral medial agranular frontal cortical field (AGm) in the rat. This cortical region is known to project bilaterally to the dorsal lateral head of the caudate-putamen of rats. Ipsilateral stimulation of AGm should excite all types of corticostriatal neurons projecting to neostriatal neurons in the corresponding area in neostriatum, while stimulation of the same cortical area on the side contralateral to the recording should evoke synaptic potentials from a more restricted subpopulation of crossed corticostriatal neurons. Neostriatal neuronal responses were recorded intracellularly and spiny projection neurons identified by intracellular staining with horseradish peroxidase. The initial EPSP response to contralateral stimulation was similar to that evoked from the ipsilateral side, except for the absence of a relatively small short latency component responsible for the earliest part of the response to ipsilateral cortical stimulation. Comparison with previous findings indicated that this earliest EPSP component was due to activation of fast-conducting descending cortical efferents with collateral projections exclusively to the ipsilateral neostriatum. Stimulation of contralateral neostriatum evoked responses identical to those obtained using stimulation of contralateral neocortex. Analyses of these responses indicated that both EPSPs arise from activation of the same population of fibers. Stimulation of the contralateral internal capsule just caudal to neostriatum was not effective in evoking the EPSP. Chronic hemidecortication did not change the shape of the EPSP evoked from the intact contralateral side, but reduced its amplitude by approximately one half. These observations indicate that contralaterally projecting corticostriatal neurons in the rat project bilaterally in neostriatum, have axonal branches to the contralateral cerebral cortex as well as neostriatum, and converge onto neostriatal neurons that also receive input from the corresponding cortical region on the ipsilateral side.     

Inhibition of the human primary motor area by painful heat stimulation of the skin.

OBJECTIVE: To prove whether painful cutaneous stimuli can affect specifically the motor cortex excitability. METHODS: The electromyographic (EMG) responses, recorded from the first dorsal interosseous muscle after either transcranial magnetic or electric anodal stimulation of the primary motor (MI) cortex, was conditioned by both painful and non-painful CO2 laser stimuli delivered on the hand skin. RESULTS: Painful CO2 laser stimuli reduced the amplitude of the EMG responses evoked by the transcranial magnetic stimulation of both the contralateral and ipsilateral MI areas. This inhibitory effect followed the arrival of the nociceptive inputs to cerebral cortex. Instead, the EMG response amplitude was not significantly modified either when it was evoked by the motor cortex anodal stimulation or when non-painful CO2 laser pulses were used as conditioning stimuli. CONCLUSIONS: Since the magnetic stimulation leads to transynaptic activation of pyramidal neurons, while the anodal stimulation activates directly cortico-spinal axons, the differential effect of the noxious stimuli on the EMG responses evoked by the two motor cortex stimulation techniques suggests that the observed inhibitory effect has a cortical origin. The bilateral cortical representation of pain explains why the painful CO2 laser stimuli showed a conditioning effect on MI area of both hemispheres. Non-painful CO2 laser pulses did not produce any effect, thus suggesting that the reduction of the MI excitability was specifically due to the activation of nociceptive afferents.     

Learning and memory of cue-reward association meaning by modifications of synaptic efficacy in dentate gyrus and piriform cortex

This article begins with a review of recent experiments investigating the synaptic efficacy changes occurring in rat dentate gyrus and piriform cortex during an associative olfactory task. In all these experiments, animals were trained to discriminate among an artificial cue, a patterned electrical stimulation distributed to the lateral olfactory tract associated with a water reward, and a natural odor associated with a flash of light. Monosynaptic field potential responses evoked by single electrical stimuli to the lateral olfactory tract were recorded in the ipsilateral piriform cortex before and just after each training session. Monosynaptic field and polysynaptic field potentials evoked by single electrical stimuli applied respectively to the lateral perforant pathway and lateral olfactory tract were also recorded in ipsilateral dentate gyrus. The results showed an increase in synaptic efficacy subsequent to the first training session in the dentate gyrus network when compared with piriform cortex at the later stage of the learning. The early increase of monosynaptic response in the dentate gyrus was observed immediately after the first learning session but disappeared 24 h later. Inversely, a synaptic depression developed across sessions, becoming significant at the onset of the last (fifth) session. The polysynaptic potential recorded in this structure increased substantially when rats began to discriminate the leaming cues, usually after the second or third learning session. Then, from the third to the fifth session, an LTP like-phenomenon appeared in piriform cortex when rats perfectly mastered the associations. Experiments using high-frequency stimulation to prevent changes in gyrus dentatus indicated that the onset of the observed depression was necessary for the learning of the olfactory associations. The fact that hippocampal and cortical neuronal networks exhibited different timing in synaptic efficacy changes could physiologically explain learning and memory processes.     

Effects of adenosine and related compounds on an inhibitory process in rat cerebral cortex

Inhibition of neurons in the rat cerebral cortex was evoked by local cortical stimulation. Adenosine, AMP, and ATP applied by microiontophoresis produced no change of this inhibition. Theophylline and aminophylline, administered intravenously or iontophoretically, blocked the depression of neuronal firing by adenosine, but did not themselves affect the duration of inhibition. Dipyridamole and hexobendine, at iontophoretic doses which potentiated responses to adenosine, produced some reduction of inhibitory duration. We conclude that endogenous purines do not normally contribute to local cortical inhibition, but that their accumulation can inhibit this phenomenon, possibly presynaptically.     

Interaction of serotonin with somatosensory cortical neuronal responses to afferent synaptic inputs and putative neurotransmitters

The present study was conducted to investigate the action of serotonin (5-HT) on synaptic transmission within local circuits of the rat somatosensory cortex. Responses of single somatosensory cortical neurons to activation of excitatory and inhibitory synaptic pathways or iontophoretic application of putative neurotransmitters were examined before, during and after microiontophoresis of 5-HT. Monoamine-induced changes in neuronal responsiveness were quantitatively assessed by computer-based analysis of peri-event histograms. 5-HT typically exerted a differential inhibitory effect on neuronal firing, such that stimulus-induced responses were reduced relative to spontaneous discharge. In 16 of 24 (67%) of the cells tested, 5-HT depressed synaptically evoked excitation more than background firing such that "signal to noise" ratio was decreased. In some cases evoked spiking was reduced from control levels at doses of 5-HT subthreshold for producing direct depression of baseline firing rate. Cortical neuron excitatory responses to iontophoretically applied acetylcholine (8 of 13 cells) and glutamate (10 of 15 cells) were also reduced during microiontophoresis of 5-HT. A similar reduction in inhibitory efficacy was observed in 62% of the cases (10 of 16 cells) where 5-HT was interacted with GABA-induced depressant responses. Local administration of 5-HT also resulted in an antagonism of stimulus bound inhibition of firing (9 of 11 cells). These results are contrasted with previously observed facilitory effects of norepinephrine (NE) on cortical neuronal responsiveness to afferent synaptic inputs and putative transmitter agents. It is suggested that endogenously released 5-HT and NE may exert complementary modulatory-type actions on neuronal responsiveness as a means of regulating the transfer of sensory information through local cerebrocortical circuits.     

Acetylcholine and cortical excitation by pyramidal tract collaterals

Those neurons in the sensorimotor cortex of cats which fired orthodromic discharges in response to stimulation of the peduncular pyramidal tract showed a similar excitability to microiontophoretically applied acetylcholine as did other neurons not giving such a response. Atropine and scopolamine antagonized this acetylcholine effect, but neither of these muscarinic cholinolytics nor the nicotinic acetylcholine antagonist, d-tubocurarine, blocked the orthodromic responses to pyramidal stimulation even though the former agents blocked the excitatory responses to stimulation of the mesencephalic reticular formation in some acetylcholine-excited neurons. A depressant effect of acetylcholine was uncommon and unrelated to the depression commonly seen after the pyramidal stimulus. These results suggest that acetylcholine is not a synaptic transmitter of the orthodromic response to pyramidal stimulation, presumably mediated through recurrent collaterals, but that acetylcholine may transmit the excitation of some cortical neurons by reticular stimulation.     

Neurochemical stimulation of the rat substantia innominata increases cerebral blood flow (but not glucose use) through the parallel activation of cholinergic and non-cholinergic pathways

Neurochemical activation of the substantia innominata (SI) in the rat, through the direct injection of the cholinergic agonist carbachol, has been reported to induce large increases in cerebral blood flow (CBF) throughout cortical and subcortical projection regions. The present study aimed to determine whether the vasomotor responses to cholinergic stimulation of the SI were, or were not, the consequence of an increase in metabolic activity. To this end, coupled measurements of CBF and cerebral glucose use (CGU) were undertaken during carbachol-elicited stimulation of the SI. Infusion of carbachol into the basal forebrain induced significant CBF increases in several ipsilateral cortical and subcortical areas including the amygdala. In contrast, CGU increased only in the ipsilateral amygdala and SI. Thus, we tested the hypothesis of a direct neurogenic, rather than metabolic, contribution of the basalocortical system. In this respect, carbachol-elicited stimulation resulted in significant increases in extracellular acetylcholine concentrations in the ipsilateral parietal cortex; systemic pretreatment with the muscarinic receptor antagonist scopolamine completely abolished the increase in cortical CBF elicited by cholinergic stimulation of the SI in the ipsilateral frontoparietal motor cortex while it failed to affect the increase observed in the ipsilateral temporal cortex. Several conclusions can be drawn from the present study. The stimulation of the SI by carbachol induces an increase in CBF that can be dissociated from changes in underlying glucose metabolism. Secondly, these induced changes in cortical CBF are paralleled by an increase in acetylcholine release. Lastly, the failure of scopolamine to block the flow response in all cortical regions would suggest that SI stimulation will evoke the release of vasodilatatory neurotransmitter(s) as well as acetylcholine itself.     

Neuropharmacology of the nucleus accumbens: Iontophoretic applications of morphine and nicotine have contrasting effects on single-unit responses evoked by ventral pallidal and fimbria stimulation

Extracellular recordings within the nucleus accumbens (NAS) of halothane anesthetized rats have revealed that iontophoretically applied morphine and nicotine have contrasting effects on neuronal responses evoked by fimbria or VP stimulation. Iontophoretically applied morphine inhibited NAS single-unit responses evoked by VP stimulation but did not affect unit responses evoked by fimbria stimulation. In contrast, iontophoretically applied nicotine had no effect on NAS single-unit responses evoked by VP stimulation but inhibited single-unit responses evoked by fimbria stimulation. Spontaneously active NAS units were inhibited by iontophoretically applied morphine but were unaffected by nicotine. In addition, experiments were conducted to determine whether NAS unit responses to electrical stimulation of the VP were likely to involve cell body as opposed to axonal activations. Selective cell body stimulation by glutamate microinfusions into the VP region excited spontaneously active VP single-units. Concurrently recorded NAS unit responses to electrical stimulation of the VP were also excited. These results are consistent with the idea that NAS evoked responses to VP electrical stimulation involve somal activation. Generally, these results suggest a specific neuropharmacological organization of the NAS. Analysis of the effects of morphine and nicotine on other NAS circuits will establish a systems level understanding of NAS responses to reinforcers. © 1995 Wiley-Liss, Inc.     

Depression of cortical Na, K-ATPase acticvity in rats exposed to hyperbaric oxygen

Extracellular single unit recordings were used to study inhibitory synaptic responses evoked from preoptic-anterior hypothalamic neurones following arcuate-ventromedial stimulation. Intravenously administered methohexitone, pentobarbitone and thiopentone increased the duration of inhibitory synaptic responses by up to 400%. Submaximal responses to iontophoretically applied GABA but not glycine were also potentiated. Recovery from the actions of the short acting barbiturates was observed.     

A barbiturate evoked intensification of postsynaptic inhibition in the preoptic ovulatory trigger region of the hypothalamus

Extracellular single unit recordings were used to study inhibitory synaptic responses evoked from preoptic-anterior hypothalamic neurones following arcuate-ventromedial stimulation. Intravenously administered methohexitone, pentobarbitone and thiopentone increased the duration of inhibitory synaptic responses by up to 400%. Submaximal responses to iontophoretically applied GABA but not glycine were also potentiated. Recovery from the actions of the short acting barbiturates was observed.     

Optogenetic stimulation of GABA neurons can decrease local neuronal activity while increasing cortical blood flow

We investigated the link between direct activation of inhibitory neurons, local neuronal activity, and hemodynamics. Direct optogenetic cortical stimulation in the sensorimotor cortex of transgenic mice expressing Channelrhodopsin-2 in GABAergic neurons (VGAT-ChR2) greatly attenuated spontaneous cortical spikes, but was sufficient to increase blood flow as measured with laser speckle contrast imaging. To determine whether the observed optogenetically evoked gamma aminobutyric acid (GABA)-neuron hemodynamic responses were dependent on ionotropic glutamatergic or GABAergic synaptic mechanisms, we paired optogenetic stimulation with application of antagonists to the cortex. Incubation of glutamatergic antagonists directly on the cortex (NBQX and MK-801) blocked cortical sensory evoked responses (as measured with electroencephalography and intrinsic optical signal imaging), but did not significantly attenuate optogenetically evoked hemodynamic responses. Significant light-evoked hemodynamic responses were still present after the addition of picrotoxin (GABA-A receptor antagonist) in the presence of the glutamatergic synaptic blockade. This activation of cortical inhibitory interneurons can mediate large changes in blood flow in a manner that is by and large not dependent on ionotropic glutamatergic or GABAergic synaptic transmission. This supports the hypothesis that activation of inhibitory neurons can increase local cerebral blood flow in a manner that is not entirely dependent on levels of net ongoing neuronal activity.     

Development of contralateral and ipsilateral frequency representations in ferret primary auditory cortex

Little is known about the maturation of functional maps in the primary auditory cortex (A1) after the onset of sensory experience. We used intrinsic signal imaging to examine the development of the tonotopic organization of ferret A1 with respect to contralateral and ipsilateral tone stimulation. Sound-evoked responses were recorded as early as postnatal day (P) 33, a few days after hearing onset. From P36 onwards, pure tone stimuli evoked restricted, tonotopically organized patches of activity. There was an age-dependent increase in the cortical area representing each octave, with a disproportionate expansion of cortical territory representing frequencies > 4 kHz after P60. Similar tonotopic maps were observed following stimulation of the contralateral and ipsilateral ears. During the first few weeks following hearing onset, no differences were found in the area of cortical activation or in the magnitude of the optical responses evoked by stimulation of each ear. In older animals, however, contralateral stimuli evoked stronger responses and activated a larger A1 area than ipsilateral stimuli. Our findings indicate that neither the tonotopic organization nor the representation of inputs from each ear reach maturity until approximately 1 month after hearing onset. These results have important implications for cortical signal processing in juvenile animals.     

Biochemical evidence for glutamate and/or aspartate as neurotransmitters in fibers from the visual cortex to the lateral posterior thalamic nucleus (pulvinar) in rats

The effects of visual cortex ablation on several neurotransmitter parameters in the lateral posterior thalamic nucleus (pulvinar) in rats have been investigated. We found a 57% decrease in high affinity uptake ofd-[³H]aspartate in the pulvinar after ablation of the ipsilateral visual cortex. The KCl-evoked release of exogenousd-[³H]aspartate and endogenous glutamate were decreased by 33 and 37%, respectively. Moreover, the contents of endogenous glutamate and aspartate were decreased by 35%, each. The glutamate decarboxylase and choline acetyltransferase activities and the contents of other amino acids were not affected by the lesion. Our biochemical data indicate that glutamate and/or aspartate may be transmitters in the fibers from visual cortex to pulvinar in rats.     

The cerebellar control of accomodation of the eye in the cat

The effect of cerebellar stimulation on the accomodation of the lens was examined in anesthetized cats. An infrared optometer was used to measure the refractive power of the lens during stimulation of the cerebellum. The area giving responses within latencies shorter than 160 msec and amplitudes larger than 0.15 diopters is localized in the contralateral interpositus and fastigial nuclei and the ipsilateral interpositus nucleus. No responses could be evoked by stimulating the bilateral lateral nuclei. Accomodation responses were also evoked by cerebellar cortex stimulation. Accomodation responses evoked by stimulating the cerebellar nuclei were inhibited by preceding cerebellar cortical stimulation.     

Intracellular responses of caudate neurons to temporally and spatially combined stimuli

Intracellular recordings of caudate neuronal responses evoked by temporally combined stimulations of cortex, thalamus, and substantia nigra were made in the cat. Excitatory postsynaptic potentials (EPSPs) which temporally coincided were additive. EPSPs which coincided with an inhibitory postsynaptic potential (IPSP) previously evoked from the same stimulus site were enhanced. The cortical stimulus was prepotent in the sense that EPSPs evoked from thalamic or nigral stimulation were inhibited by the cortical IPSP. The cortical EPSP was enhanced if it was evoked during a nigral or thalamic IPSP. These results are discussed in the context of recent reports concerning the fine structure of synaptic contacts of input fibers to the caudate nucleus.     

Excitatory Amino Acid Pathway from the Hippocampus to the Prefrontal Cortex. Contribution of AMPA Receptors in Hippocampo-prefrontal Cortex Transmission

Previous experiments in the rat have demonstrated that field CA1 and the subiculum project to the prefrontal cortex and that this direct unilateral pathway is excitatory. In the present study, anatomical and electrophysiological approaches were used to determine the transmitter mediating the excitatory responses in prefrontal cortex neurons to low-frequency stimulation of the hippocampus. The method of selective retrograde d-[3H]aspartate labelling was used to identify putative glutamatergic and/or aspartatergic hippocampal afferent fibres to the prefrontal cortex. Unilateral microinjection of d-[3H]aspartate into the prelimbic area of the prefrontal cortex resulted in the retrograde labelling of a fraction of hippocampal neurons. Some labelled cell bodies were distributed in field CA1 and the subiculum but larger numbers of neurons were detected in the ventral and intermediary subiculum. In a second series of experiments, the excitatory transmission from the hippocampus to the prefrontal cortex was pharmacologically analysed to provide further evidence for the involvement of glutamate and/or aspartate in the pathway. All prefrontal cortex neurons responding to the stimulation of the hippocampus were activated by selective agonists of the glutamate receptor subtypes alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-d-aspartate (NMDA), and these effects were selectively antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (APV) respectively. Most of the excitatory responses of prefrontal cortex neurons to single and paired-pulse stimulation of the hippocampus were antagonized by CNQX. APV only affected the excitatory response in a few cells. These results suggest that the hippocampal input to the prefrontal cortex utilizes glutamate and/or aspartate as a transmitter. Even though prefrontal cortex neurons responding to the stimulation of the hippocampus appear to have both AMPA and NMDA receptors, low-frequency stimulation of the hippocampo-prefrontal cortex pathway activates cortical neurons mostly through AMPA receptors.