On the possible functional role of afferent pathways in skin sensation

Single unit activity was recorded from postcentral gyrus (SI) neurons in chronically prepared macaque monkeys. Lesions of the dorsal funiculi (especially cuneatus), or the lateral lemniscus (at the mesencephalic level) failed to significantly modify the properties of the cortical responses to peripheral stimuli, while combined lesions of both pathways were quite effective in this regard. An additional finding was that combined “deafferentation” of a hemisphere caused a significant proportion of cells in it to respond to ipsilateral stimuli. We conclude that both the medial lemniscal and spinothalamic pathways carry information—in parallel—to the cortex, that this information is conveyed in two modes by each pathway (“elemental” and “convergent”) and that ipsilateral inputs relayed to SI are revealed by partial deafferentation of its contralateral inputs.     

Taste responses in the superior secondary gustatory nucleus of the carp, cyprinus carpio L.

Single unit discharges in the superior secondary gustatory nucleus of the carp, Cyprinus carpio L., were studied electrophysiologically in response to chemical stimulation of the external chemoreceptors of the facial skin surface.Of 36 gustatory neurons recorded, 80.6% were facilitated by taste stimuli and 19.4% were inhibited. The gustatory neurons were classified according to their responsiveness to the 4 basic taste substances and, except the inhibitory type, did not differ remarkably from the primary and secondary gustatory neurons. More inhibitory type (19.4%) neurons occurred at higher levels of the gustatory system. As in the primary and secondary levels, sodium chloride and acetic acid solutions were more effective stimuli than quinine HCl and sucrose.The ascending secondary gustatory fibers project bilaterally to the superior gustatory nucleus of the carp. About 20% of the gustatory neurons respond to stimulation of only the contralateral facial skin while 27.8% respond to stimulation of either side of the face. The latter neuron type showed very complicated responses, and were classified into ‘Uniform’, ‘Summation’, ‘Contra.Ipsi.’ and ‘Quality field’ types. The remaining 50% of the neurons respond only to stimulation on the ipsilateral side.     

Cholinergic properties of neurons differentiated from an embryonal carcinoma cell-line (P19)

P19 is a mouse-derived embryonal carcinoma cell-line capable of differentiation toward ectodermal, mesodermal and endodermal lineages. Following treatment with retinoic acid these cells differentiated into neurons, astrocytes and fibroblast-like cells.We induced P19 differentiation under conditions which lead to a homogeneous neuronal culture (> 95% neurons). Under these conditions, most cells (85%) express high levels of the cholinergic markers acetyl cholinesterase and choline acetyltransferase while 10% of cells express the GABAergic marker glutamic acid decarboxylase. While the proportion of the GABAergic neurons is constant at different culture conditions, the cholinergic phenotype is suppressed at high cell densities. The cholinergic nature of P19 neurons is also evident in their ability to form contacts with a muscle cell-line — C2. At day 10 of differentiation cells are capable of depolarization-dependent acetylcholine release. The release is Ca²⁺ dependent, and drops to baseline levels at 0.5 mM Ca²⁺. The cells also respond to sub-nM levels of α-latrotoxin by acetylcholine release. All major proteins implicated in synapse functionality are expressed prior to day 10 at both at RNA and protein levels. However, the expression pattern of each gene is unique. The genes include cytoskeletal proteins, synaptic vesicle proteins and terminal specific proteins.We suggest that this cell-line can serve as an in-vitro model system for the study of neuronal phenotype acquisition. Under our conditions, the P19 cells can also provide a system in which to study the differentiation of functional cholinergic neurons.     

Selective depletion of somatostatin in rat brain by cysteamine

A single injection of cysteamine (300 mg/kg, subcutaneously) results in a 70–80% decrease in somatostatin levels in the periventricular nucleus where somatostatin-producing neurons are located and the median eminence where somatostatinergic nerve terminals are. The drug seems quite selective: no changes in levels of other neuropeptides — LH-RH, vasopressin, enkephalin, VIP, CCK — were observed in the same animals.     

Responses of neurons of the parietal association cortex of the cat to acoustic stimulation before and after suppression of the auditory cortex in the cat

The aim of this work was to study the influence of auditory cortex suppression in cat on response patterns of the parietal associative cortex neurons responding to different frequency tones. Suppression was performed by two methods: bilateral isolation and application of 6% nembutal solution on the cortex surface. Frequency-thresholds curves were plotted for all neurons studied. Prior to suppression the majority (84%) of studied neurons had one or two characteristic frequencies. After suppression the percentage of such cells fell to 63% of all responding neurons. Frequency range to which neurons could respond was altered as well. Normally almost all neurons tested could respond to a wide spectrum of presented frequencies. After suppression 69% of neurons did not respond to tones above 8-10 kHz. This may indicate that mainly information about high frequency tones is transmitted via the auditory cortex. The possibility that associative thalamic nuclei are the main source of acoustic information for parietal associative cortex neurons is discussed.     

Ontogeny of tonotopic organization of brain stem auditory nuclei in the chicken: implications for development of the place principle

The morphological development of the cochlea begins in the base or midbasal region and spreads toward the apex. In adults, the base responds maximally to high-frequency sounds and lower frequencies are represented progressively toward the apex. This predicts that responses to sound should occur initially to high frequencies and gradually change to include lower frequencies. Paradoxically, animals respond first to relatively low frequencies and last to high frequencies. We have previously proposed that this discrepancy results from an ontogenetic change in spatial coding of frequency along the cochlea (Rubel et al., '76). According to this model, only the basal end of the cochlea transduces sound early in development but it responds to low frequencies. During maturation the representation of low and midrange frequencies shifts apically and the base becomes responsive to high frequencies. This hypothesis predicts that the tonotopic organization within the central nervous system should change during development; neurons at any given location within an auditory nucleus should become maximally responsive to successively higher frequency sounds during development. In the present study this prediction was tested by using microelectrode recording procedures to map the tonotopic organization of nucleus magnocellullaris (NM) and nucleus laminaris (NL), first- and second-order auditory nuclei, in chickens at three ages: embryonic day 17, 1 day posthatch, and 2-4 weeks posthatch. The characteristic frequencies of neurons having the same anatomical location were quantitatively compared across ages. The tonotopic order in NM and NL was similar at all ages; responses to high-frequency sounds were recorded anteromedially and lower frequencies were located progressively more caudolaterally. However, there was a striking quantitative change in tonotopic organization. Neurons at a given location in both nuclei became maximally responsive to progressively higher frequencies during development. The characteristic frequencies of neurons in embryos and newly hatched chicks averaged, respectively, 1.00 (+/- 0.06, S.E.M.) and 0.34 (+/- 0.04) octaves lower than their predicted adult values. All regions in both nuclei showed a statistically significant increase in characteristic frequency during development except the most posterolateral (low-frequency) sector. Too few neurons were recorded from this region to be able to reliably estimate characteristic frequency. These results support the hypothesis that the spatial coding of frequency along the cochlea shifts during development.(ABSTRACT TRUNCATED AT 400 WORDS)     

Nucleus accumbens to globus pallidus GABA projection: Electrophysiological and iontophoretic investigations

Extracellular recordings were obtained from neurons in the nucleus accumbens and globus pallidus of urethane anesthetized rats. Eight neurons in the nucleus accumbens were activated antidromically following stimulation of the globus pallidus. Calculated conduction velocities were 0.4–1.5 m/sec, indicative of small unmyelinated fibers.A total of 74 of 153 neurons in the globus pallidus responded to stimulation of the nucleus accumbens. Of these neurons 4 (2.7%) were excited only, 46 (30.1%) were inhibited only and 24 (15.7%) had sequential effects of excitation and inhibition. Iontophoretic application of picrotoxin was found to attenuate or abolish the poststimulus inhibition in one-half of the neurons examined. The 74 neurons which responded to stimulation of the nucleus accumbens had slower firing frequencies and generally more random firing patterns than neurons which did not respond to stimulation. Fifty-three per cent of all globus pallidus neurons examined had increased spontaneous firing frequencies following the iontophoretic administration of picrotoxin alone. This is indicative of the removal of a tonic GABA input onto these neurons. Most neurons examined had decreased spontaneous firing frequencies following the iontophoretic application of GABA which could be blocked by the iontophoretic application of picrotoxin.The results from antidromic activation, slow conduction velocity, sensitivity to GABA and picrotoxin, and picrotoxin attenuation of the poststimulus inhibitory effect provide evidence of a direct GABAergic projection from the nucleus accumbens to the globus pallidus in the rat.     

Segregation of stimulus phase and intensity coding in the cochlear nucleus of the barn owl

The cochlear nucleus of the barn owl is composed of two anatomically distinct subnuclei, n. magnocellularis (the magnocellular nucleus) and n. angularis (the angular nucleus). In the magnocellular nucleus, neurons tend to respond at a particular phase of a stimulus sine wave. Phase locking was observed for frequencies up to 9.0 kHz. The intensity-spike count functions of magnocellular units are characterized by high rates of spontaneous activity, a narrow range of intensities over which spike counts changed from spontaneous to saturation levels, and a small increase in spike counts with intensity over that range. In the angular nucleus, neurons showed little or no tendency to respond at a certain sinusoidal phase, although some showed weak phase locking for frequencies below 3.5 kHz. Angular units typically had low spontaneous rates, large dynamic ranges, and large increases in spike counts with intensity, resulting in high saturation levels. The clear difference between the two nuclei in sensitivity to both phase and intensity and the reciprocity in response properties support the hypothesis that each nucleus is specialized to process one parameter (phase or intensity) and not the other.     

The effects of noxious heat on responses of spinocervical units to low intensity cutaneous stimuli

The responses of spinocervical neurons to sinusoidal hair displacements were studied during and in the absence of radiant heating of parts of the hindpaw to noxious levels (45–65 °C). Noxious heat usually increased background discharge and lowered the signal-to-noise ratio at low frequencies of hair displacement. At higher frequencies over 20 Hz, this ratio was slightly depressed for half of the cells, and dramatically increased for the others. Similar effects were found when the heating was off the receptive field for hair displacement, which suggests a central cause for these effects.     

On the use of spatial frequency to isolate contributions from the magnocellular and parvocellular systems and the dorsal and ventral cortical streams

Many authors have claimed that suprathreshold achromatic stimuli of low and high spatial frequency can be used to separate responses from different entities in the visual system. Most prominently, it has been proposed that such stimuli can differentiate responses from the magnocellular and parvocellular systems. As is reviewed here, investigators who have examined stimulus specificity of neurons in these systems have found little difference between magno- and parvocellular cells. It has also been proposed that spatial frequency can be used to selectively activate the “magnocellular-dorsal stream”. The present review indicates that cells in Area MT of the dorsal stream do prefer very low spatial frequencies. However, the review also shows that cells in Area V4 of the ventral stream respond, not only to relatively high spatial frequencies, but also to low frequency stimuli. Thus, low spatial frequencies cannot be relied upon to selectively activate the dorsal stream.     

Etorphine elicits anomalous excitatory opioid effects on sensory neurons treated with GM1 ganglioside or pertussis toxin in contrast to its potent inhibitory effects on naive or chronic morphine-treated cells

The ultra-potent opioid analgesic, etorphine, elicits naloxone-reversible, dose-dependent inhibitory effects, i.e. shortening of the action potential duration (APD) of naive and chronic morphine-treated sensory dorsal root ganglion (DRG) neurons, even at low (pM-nM) concentrations. In contrast, morphine and most other opioid agonists elicit excitatory effects, i.e. APD prolongation, at these low opioid concentrations, require much higher (ca. 0.1–1 μM) concentrations to shorten the APD of naive neurons, and evoke only excitatory effects on chronic morphine-treated cells even at high > 1–10 wM concentrations. In addition to the potent agonist action of etorphine at μ-, δ- and κ-inhibitory opioid receptors in vivo and on DRG neurons in culture, this opioid has also been shown to be a potentantagonist of excitatory μ-, δ- and κ-receptor functions in naive and chronic morphine-treated DRG neurons. The present study demonstrates that the potent inhibitory APD-shortening effects of etorphine still occur in DRG neurons tested in the presence of a mixture of selective antagonists that blocks all μ-, δ- and κ-opioid receptor-mediated functions, whereas addition of the epsilon (ε)-opioid-receptor antagonist, β-endorphin(1–27) prevents these effects of etorphine. Furthermore, after markedly enhancing excitatory opioid receptor functions in DRG neurons by treatment with GM1 ganglioside or pertussis toxin, etorphine showsexcitatory agonist action onnon-μ-/δ-/κ-opioid receptor functions in these sensory neurons, in contrast to its usual potent antagonist action on μ-, δ- and κ-excitatory receptor functions in naive and even in chronic morphine-treated cells which become supersensitive to the excitatory effects of μ-, δ- and -opioid agonists. This weak excitatory agonist action of etorphine on non-μ-/δ-/κ-opioid receptor functions may account for the tolerance and dependence observed after chronic treatment with extremely high doses of etorphine in vivo.     

Activation of 5-HTIB receptors suppresses low but not high frequency synaptic transmission in the rat subicular cortex in vitro

We have shown previously that activation of 5-HT_1B serotonin receptors mediates suppression of the amplitude of evoked potentials in the subiculum [2]. Here we show that after application of 5-HT (10 μM), excitatory postsynaptic potentials of subicular neurons have reduced amplitudes with no change in membrane potential, input resistance and postynaptic fiber volleys. These results suggest that activation of 5-HT_1B receptors reduces the release of glutamate from incoming fibers originating from CA1 pyramidal cells. In presence of 5-HT (10 μM), theta patterned stimulation still induced LTP, similar to that observed in control slices. Application of similar concentrations of 5-HT during double pulse stimulation (interval 10–15 ms) reduced the response to the first pulse (repetition interval 30 s), but the response to the second pulse of the pair was unaffected. We propose that 5-HT_1B receptor activity suppresses subicular transmission at low but not at high frequencies.     

Long-term potentiation as a function of test pulse intensity: A study using input/output profiles

Input/output profiles of the population responses in CA1 were recorded in the rat hippocampal slice in vitro following stimulation of the Schaffer collaterals before and after theta-frequency patterned primedbursts (PBs). The most robust potentiation was found for the population spike amplitude, which reached > 200% at low intensity test pulses, but decreased at high intensity. The latency of the population spike was more consistently decreased at high than low stimulus intensities. The enhancement of the population dendritic EPSPs was larger at low than high intensity. Intracellular recordings from CA1 neurons indicated that the intracellular and population EPSPs showed a similar saturation with stimulus intensity, while all single neurons fired at 60 μA intensity when the population spike only reached a mean 70% of its maximal amplitude, suggesting that population spike increase at > 60 μA intensity or following potentiation was caused by increased firing synchrony among neurons. It is suggested that input/output profiles are necessary for the standardization of the degree of longterm potentiation among different laboratories.     

Cutaneous temperature and unit activity in the hypothalamic thermoregulatory centers

Multiple and single unit activity has been recorded in the preoptic/anterior hypothalamic nuclei of rats anesthetized with urethane. Two groups of neurons have been identified within the medial and lateral regions of the rostral hypothalamus which exhibit changes in their spontaneous discharge frequencies in a similar manner to the frequency characteristics of either “warm” or “cold” cutaneous thermoreceptors. It is suggested that the change in frequency of discharge of these neurons may represent the neural correlate of the downward setting of the hypothalamic thermostat that occurs when the animal is exposed to elevated environmental temperatures.     

Quantitative light microscopic autoradiographic localization of α2-adrenoceptors in the human brain

In the present work the anatomical distribution of α₂-adrenoceptors in the human central nervous system was studied in detail by quantitative autoradiography using the selective α₂ agonist [³H]bromoxidine ([³H]UK-14304) as a ligand. Only postmortem tissues from subjects free of neurological disorders were used in this study. Very high or high densities of α₂-adrenoceptors were found along layers I and III in non-visual neocortex, layers III and IVc of the visual cortex, CA₁ field — stratum lacunosum-moleculare — and dentate gyrus — stratum granularis — at the hippocampal formation, nucleus arcuatus at the hypothalamus, locus ceruleus, nucleus dorsalis of vagus and at the stratum granularis of the cerebellar cortex. Relevant densities of α₂-adrenoceptors were also observed along the remaining layers of neocortex, nuclei centralis, medialis and corticalis at the amygdala, anterior thalamic group and rotundocellularis nuclei, paraventricular and ventromedial hypothalamic nuclei, substantia innominata, superior colliculus — stratum zonale — and lateral periaqueductal area at the midbrain, nucleus tractus solitarii and dorsal horn — substantia gelatinosa — of the spinal cord. [³H]Bromoxidine specific binding was very low or negligible in the remaining brain areas. Although a general parallelism between the distribution of these receptors could be observed for the rat and human brain, dramatic species differences in the level of α₂-receptors were found in several brain areas, such as thalamus, amygdala or cerebellar cortex. In general, the distribution of α₂-adrenoceptors in the human brain found here was parallel to that described for the noradrenergic presynaptic terminals in the mammalian central nervous system, lending some weight to the proposed predominant presynaptic localization of these receptors. The relevance of the anatomical distribution of α₂-adrenoceptors in the human brain for a better knowledge of the neurochemistry of neuropsychiatric disorders is discussed.     

Kainate-induced lesion in the optic tectum: dependency upon optic nerve afferents or glutamate

Kainic acid is known to induce characteristic lesions in neurons receiving an intact input with presumed glutamate-mediated neurotransmission. There are indications for glutamate as a transmitter of retinal afferent terminals in the pigeon optic tectum. After tectal injection of kainic acid (0.5–2.0 μg in 0.5 μl) the optic tectum was studied by light and electron microscopy and the following changes were observed: (a) within 1–48 h important neuropil vacuolization predominantly in lower part of layer 5. Such vacuoles were sometimes postsynaptic to identified retinal afferent terminals: (b) within 1 h to 21 days progressive neuronal cell loss throughout the tectal layers. These toxic effects were not observed 2–12 weeks after contralateral retinal ablation but could partially be restored by combined glutamate (0.2 mg) and kainate injection. Thus in the pigeon tectum, kainic acid neurotoxicity is dependent upon an intact retinal input, a finding consistent with a special role for glutamate — possibly as a transmitter — in retinal terminals.     

Dopamine modulates carotid nerve responses induced by acetylcholine on the cat petrosal ganglion in vitro

We have recently reported that application of acetylcholine (ACh) or nicotine to the petrosal ganglion—the sensory ganglion of the glossopharyngeal nerve—elicits a burst of discharges in the carotid nerve branch, innervating the carotid body and sinus, but not in the glossopharyngeal branch, innervating the tongue and pharynx. Thus, the perikarya of sensory neurons for the carotid bifurcation exhibit selective cholinosensitivity. Since dopamine (DA) modulates carotid nerve chemosensory activity, we searched for the presence of DA sensitivity at the perikarya of these neurons in the cat petrosal ganglion superfused in vitro. Applications of DA in doses of up to 5 mg to the ganglion did not modify the rate of spontaneous discharges in the carotid nerve. However, if DA was applied 30 s before ACh injections, ACh-evoked reactions were modified: low doses of DA enhanced the subsequent responses to ACh, while high doses of DA depressed the responses to ACh. This depressant effect of DA on ACh responses was partially antagonized by adding spiroperone to the superfusate. Our results show that the response to ACh of petrosal ganglion neurons projecting through the carotid nerve is modulated by DA acting on D₂ receptors located in the somata of these neurons. Thus, dopaminergic modulation of cholinosensitivity could be shared also by the membranes of peripheral endings and perikarya of primary sensory neurons involved in arterial chemoreception.     

GABA and bicuculline actions on mouse spinal cord and cortical neurons in cell culture

The neutral amino acid γ-aminobutyric acid (GABA) produced membrane hyperpolarization and increased membrane chloride ion conductance of spinal cord (SC) and cortical (CTX) neurons in cell culture. GABA dose-response curves were obtained for SC neurons by pressure applying known concentrations of GABA from micropipettes with large tips (miniperfusion pipettes). GABA response threshold was about 2 μM and large responses were elicited at GABA concentrations greater than 10 μM. Bicuculline (BICUC) (0.1–10 μM) reversibly antagonized GABA responses on both SC and CTX neurons with a half maximal inhibitory concentration of about 1 μM. BICUC antagonism of GABA responses was competitive (Lineweaver-Burke analysis). These results are compared with data on GABA and BICUC displacement of [³H]GABA binding to membranes of SC and CTX neurons in cell culture. It is suggested that high affinity GABA receptors are likely to be relevant for postsynaptic GABA responses while low affinity GABA receptors may be presynaptic.     

Lateral geniculate neuron responses to drifting sine-wave gratings in rabbits

Neurons of the lateral geniculate body in rabbits were excited with drifting sine-wave gratings. Rabbits were anesthetized and paralyzed under conventional methods to record action potentials of single cells using tungsten in glass microelectrodes. All classes of geniculate cells responded in a modulatory pattern. It appears that the unmodulatory pattern typical of complex cell types of the cortex is extremely infrequent or absent. In the spatial domain most cells are low pass and bandpass. Only one unit was high pass. In the temporal domain lowpass and bandpass cells were the most frequently recorded. Four geniculate cells were high pass. It appears, therefore, that neurons of rabbits' geniculate are tuned over spatial and temporal frequencies of sine-wave gratings. The comparison with cortical recordings revealed that geniculate cells are more broadly tuned than cortical neurons. This study suggests that the rabbit's visual system is sensitive to gratings. However cells respond optimally to lower values, e.g., broader gratings, than neurons of frontalized eye animals.