Single unit activity in the auditory cortex of a monkey performing a short term memory task

Summary Short term memory to tones (STMT) was investigated by recording single unit activity in the auditory cortex of a behaving monkey. The activity of each unit was studied in two behavioral conditions: a) During task performance, the monkey had to compare two tones separated by one second of silence (inter-stimulus interval), b) During a nonperforming period; the monkey heard the two tones but did not respond behaviorally. It was noted that the firing rate of many units during the inter-stimulus interval (ISI) was dependent on the frequency of the first tone. Such dependency was observed even towards the end of the ISI, both during task performance trials (50% of the units) and during the nonperforming period (32% of the units). The activity of these units could be the basis of STMT in both of these behavioral states. In 65% of all the units tested, the responses during the ISI were of a higher magnitude in the performance period than were the responses in the non-performance period. The activity of these units may be related either to general processes such as attention and expectation or to short-term memory processes. During task performance, the responses of 23% of the units to the second tone were dependent on whether its frequency was identical to that of the first tone. Such dependency was never observed during the non-performing period. These units may detect similarity or non similarity between two tones presented one second apart. Periodic patterns of firing were not found in the study, thus suggesting that the ISI responses were not generated by reverberatory activity in simple closed loops. On the basis of these results, several alternative mechanisms of STMT are suggested.     

Pharmacological characterization of the receptor mediating the adrenergic inhibition of responses to substance P in the cingulate cortex

The excitatory responses of neurones in the anterior cingulate cortex of the rat to iontophoretically applied substance P (SP) are reduced by noradrenaline (NA) applied iontophoretically or released from noradrenergic pathways. In order to determine the receptor involved in this inhibitory effect we have studied the effects of a number of receptor-specific adrenergic agonists and antagonists on responses of cingulate neurones to SP in rats anaesthetized with chloral hydrate. Low iontophoretic currents (0-15 nA) of NA, adrenaline and the beta-agonist, clenbuterol, all strongly reduced responses to SP. Isoprenaline was also effective but less consistently so, although problems were experienced with its iontophoretic release from micropipettes. The alpha 1-agonists, phenylephrine and methoxamine were also able to reduce responses to SP. However, this reduction required higher iontophoretic currents (15-60 nA) and was associated with depressant effects on baseline firing rate. The alpha 2-agonist clonidine was only weakly active at high currents and this too was associated with depression of baseline firing. Similar weak effects were noted with dopamine. The inhibitory effects of NA on SP responses were convincingly blocked or reversed by the beta-antagonist, practolol, but not by the alpha 1-antagonist, prazosin. The reduction of SP responses by phenylephrine was also blocked by practolol but unaffected by prazosin. Finally, reduction of SP excitations by activation of the coeruleocortical pathway was also blocked by practolol applied iontophoretically to the cortical cells. These results are consistent with the hypothesis that the effect of NA on SP responsiveness in the cingulate cortex is mediated by beta-adrenoreceptors.     

Modification of the Na,K-pump of glial cells within cobalt-induced epileptogenic cortex of rat

The characteristics of a glial Na⁺,K⁺-pump dependent on extracellular K⁺ within epileptogenic cortex were studied electrophysiologically, biochemically and histochemically in vitro using slices from cobalt-induced epileptogenic cortex of rat. When the extracellular K⁺ concentration ([K⁺]_o) was varied between 4 and 40 mM, the mean slope of membrane potential plotted against [K⁺]_o was about 57 mV in glia from the normal cortex (tissue A) and about 44 mV in glia from the epileptogenic cortex (tissue B); whereas no significant difference in the resting membrane potential of these tissues was observed. In glia from tissue B, a marked transient hyperpolarization above control level was caused by replacement of elevated [K⁺]_o with the normal medium. Ouabain abolished these phenomena observed in glia from tissue B, but had no effect on the membrane potential during normal [K⁺]_o. Reduction of extracellular Na⁺, Ca²⁺ and Cl⁻ did not significantly affect the membrane potential of glia from either tissue. In tissue A, the cells marked by intracellular injection of horseradish peroxidase after intracellular recording were protoplasmic astrocytes; in tissue B, fibrous astrocytes with abnormal processes predominated. K⁺-dependent stimulation of Na⁺,K⁺-ATPase activity of the astrocyte-enriched fraction and its membrane preparation from tissue B was much larger than that from tissue A. A certain amount of the reaction product of K⁺-pNPPase activity was seen on glial plasma membrane within tissue B but not on that from tissue A. The above findings suggest that a glial Na⁺,K⁺-pump within actively firing epileptogenic cortex may be modified to increase in its activity.     

Characterization of ramified microglia in tissue culture: pinocytosis and motility

Functional properties of ramified microglia were investigated in primary cultures of rat cerebral cortical cells. These microglia could be readily identified in both fixed and living cultures through previously established features. Based on their destruction by 5 mM L-leucine methyl ester, a high level of intrinsic endocytotic activity was established. When cultures were incubated with fluorescent latex beads to assess phagocytosis, little or no such activity was exhibited by ramified cells. However, when cultures were incubated with dyes or other soluble tracer compounds, these cells always exhibited labeling. This labeling was selective for ramified microglia in the cultures and was demonstrated using a variety of compounds, including trypan blue, lucifer yellow, horseradish peroxidase (HRP), and India ink. Intracellular label could be observed in vesicular structures; this localization corresponded to an active cellular process. Also, cellular labeling was inhibited by the presence of colchicine. These features supported the inference that the labeling was attributable to pinocytosis, and this process appeared to account for the vast majority of endocytotic activity in the ramified microglia. Possible physiological significance of this pinocytotic activity was indicated by the accumulation of various neurotransmitters/modulators: gamma-aminobutyric acid and vasoactive intestinal polypeptide (VIP). Ramified cells in these cultures have been previously noted to exhibit a constant and rapid pattern of motility, which was consistently observed here through time-lapse video recording; pinocytosis and rapid motility were shown to concur in individual cells. Based on their high intrinsic pinocytotic activity and pattern of cellular motility, the ramified microglia specifically are suggested to serve a constitutive function of fluid cleansing within the interstitial spaces of brain tissue.     

Variability in hand surface representations in areas 3b and 1 in adult owl and squirrel monkeys

Detailed microelectrode maps of the hand representation were derived in cortical areas 3b and 1 from a series of normal adult owl and squirrel monkeys. While overlap relationships were maintained, and all maps were internally topographic, many map features varied significantly when examined in detail. Variable features of the hand representations among different monkeys included a) the overall shapes and sizes of hand surface representations; b) the actual and proportional areas of representations of different skin surfaces and the cortical magnifications of representations of specific skin surfaces, which commonly varied severalfold in area 3b and manyfold in area 1; c) the topographic relationships among skin surface representations, with skin surfaces that were represented adjacently in some monkeys represented in locations many hundreds of microns apart in others; d) the internal orderliness of representations; e) the completeness of representations of the dorsal hand surfaces; and f) the skin surfaces represented along the borders of the hand representation. Owl monkey maps were, in general, internally more strictly topographic than squirrel monkey maps. In both species, area 3b was more strictly topographic and less variable than was area 1. The degree of individual variability revealed in these experiments is difficult to reconcile with the hypothesis that details of cortical maps are ontogenetically specified during a period in early life. Instead, we propose that differences in the details of cortical map structure are the consequence of individual differences in lifelong use of the hands. This conclusion is consistent with earlier studies of the consequences of peripheral nerve transection and digital amputation, which revealed that cortical maps are dynamically maintained and are alterable as a function of use or nerve injury in these monkeys (Merzenich et al., '83a,b, '84a; Merzenich, '86; Jenkins et al., '84; Jenkins and Merzenich, '87).     

Effect of CNTF on low-affinity NGF receptor expression by cultured neurons from different rat brain regions.

Our previous work indicated that in E14 embryonic rat spinal cord cultures ciliary neuronotrophic factor (CNTF) exerted (1) a survival-promoting effect on motor neurons and on a large population of unidentified neurons, and (2) a regulatory role on the expression of ChAT and low affinity NGF receptor (LNGFR) in a population of small/medium-sized neurons. In the present study, we examined the effect of CNTF on the expression of LNGFR in cultures of different regions from the E18 embryonic rat brain, namely cortex, septum, striatum, mesencephalon, hippocampus, brainstem, and cerebellum. The number of LNGFR-positive neurons (stained with the 192-IgG monoclonal antibody) was determined in untreated cultures and in cultures treated for 6 days (0-6) with human recombinant CNTF. To distinguish between effects on survival and on LNGFR expression, experiments were performed in which CNTF was administered only for the last 48 h of the culture (from days 4-6). LNGFR positive neurons were found in the cultures of all the regions examined. In each one of them, CNTF increased the number of LNGFR-positive neurons by three- to fourfold after 6 days of treatment. In the striatum, septum, mesencephalon, and cerebellum, the effect of CNTF was shown to be on the regulation of LNGFR expression and not on survival. In cultures from the cortex, hippocampus and brainstem, a survival-promoting role of CNTF could be demonstrated. The effect of CNTF was dose dependent, with half-maximal effects (ED50) achieved at 2-4.5 TU/ml for all the brain regions. Maximal effects were reached at 100-250 TU/ml. From these results, we conclude that (1) there exists a wide spectrum of CNTF-responsive neurons in the central nervous system, and (2) CNTF plays an important and widespread role in regulating the expression of the LNGFR in neurons.     

Local circuit neurons of macaque monkey striate cortex: I. Neurons of laminae 4C and 5A

A study has been made, using Golgi preparations, of the organization of neurons with smooth or sparsely spined dendrites, here called local circuit neurons, of the macaque monkey primary visual cortex. Since these neurons include those responsible for inhibitory circuitry of the cortex, a better understanding of their anatomical organization is essential to concepts of functional organization of the region. This account describes those neurons found with cell body and major dendritic spread within the thalamic recipient zone of lamina 4C and its border zone with lamina 5A. The neurons are grouped firstly in terms of in which laminar division the soma occurred--4C beta, 4C alpha or the border zone of 5A-4C beta--and secondly, into varieties on the basis of the interlaminar projection patterns of their axons. Most, if not all, of the local circuit neurons of these divisions have interlaminar axon projections as well as an arbor local to their cell body and dendritic field. These interlaminar projections are highly specific, targeting from one to five laminar divisions depending on the variety of neuron; on this basis 17 varieties of local circuit neuron are described. While the number of varieties appears dauntingly large in terms of understanding the functional circuitry of the region, the clear-cut organization of the interlaminar links may provide clues as to the information processing that concerns each neuron. The local circuit neuron axon projections can be related to a wealth of information already available concerning the laminar organization of afferent axons and efferent cell groups, the organization of spiny neuron intrinsic relays (presumed to be excitatory), and physiological properties of different laminar divisions. It is hoped that the information derived from this study can serve as a guide for correlated physiological-anatomical studies on single cells of the region.     

在大鼠大脑皮质发育过程中5—HT受体亚型的改变

５－ＨＴ灌流幼年组及成年组大鼠脑片。幼年组６６．７％额叶后部Ⅳ层神经元的兴奋性突触后电位（ＥＰＳＰ）幅度降低７３．９％，膜电位和膜电阻无变化；此作用为５－ＨＴ１β激动剂ＴＦＭＰＰ模拟，为５－ＨＴ１Ａ／１β拮抗剂ｐｉｎｄｏｌｏｌ阻抑；５－ＨＴ不降低低钙高镁液中谷氨酸钠的去极化反应。提示幼年期５－ＨＴ经突触前膜５－ＨＴ１β受体抑制突触传递。５－ＨＴ灌流使成年组６０．９％神经ＥＰＳＰ降低３６．２％，伴随     

大鼠马桑内酯急性局灶型癫痫大脑运动皮质的形态计量研究

用微量马桑内酯注入Ｗｉｓｔａｒ大鼠左侧前肢运动皮质，造成急性局灶型癫痫。用光镜、电镜和体视学方法研究其运动皮质第Ｖ层结构的改变。结果显示：癫痫大鼠运动皮质灶区、灶旁区的神经细胞数和胶质细胞数均分别比对照大鼠灶区和灶旁区显著减少；灶区神经毡中突触性终末数，显著减少；突触性终末的面积分数明显减少，而树突的面积分数无变化；神经胶质突起的面积分数增加。