Unilateral deficits in visual perception and learning after unilateral inferotemporal cortex lesions in macaques

This study adapted the method of partial lesions, combined with controlled fixation, to study the perceptual role of macaque inferotemporal (IT) cortex. Unilateral lesions were made in IT cortex of three monkeys, without section of the corpus callosum, and visual function was tested ipsilateral and contralateral to the lesion. The observed changes were compared to the effects of bilateral lesions of IT cortex in one monkey, the approach used in most previous studies. Unilateral lesions produced far less profound, although more selective, loss on the tested visual abilities than did bilateral lesions. All three monkeys with unilateral lesions showed decreased chromatic sensitivity, but sparing of achromatic sensitivity, and severely disrupted learning and performance of visual matching to sample, and in all cases, the visual loss was contralateral to the site of the lesion. Unexpectedly, the magnitude of the contralateral loss was not increased by later section of the corpus callosum and anterior commissure in one of the monkeys, a lesion that removes interhemispheric input to contralateral from ipsilateral temporal cortex neurons. These results support physiological findings that show that the response of IT cortex neurons is dominated by the contralateral visual field, despite the bilateral activation many IT neurons receive. Comparison to earlier studies of lesions of area V4, which provides input to IT cortex, shows that V4 and IT lesions produce qualitatively different effects.     

Attention modulates gamma-band oscillations differently in the human lateral occipital cortex and fusiform gyrus

We studied the existence, localization and attentional modulation of gamma-band oscillatory activity (30-130 Hz) in the human intracranial region. Two areas known to play a key role in visual object processing: the lateral occipital (LO) cortex and the fusiform gyrus. These areas consistently displayed large gamma oscillations during visual stimulus encoding, while other extrastriate areas remained systematically silent, across 14 patients and 291 recording sites scattered throughout extrastriate visual cortex. The lateral extent of the responsive regions was small, in the range of 5 mm. Induced gamma oscillations and evoked potentials were not systematically co-localized. LO and the fusiform gyrus displayed markedly different patterns of attentional modulation. In the fusiform gyrus, attention enhanced stimulus-driven gamma oscillations. In LO, attention increased the baseline level of gamma oscillations during the expectation period preceding the stimulus. Subsequent gamma oscillations produced by attended stimuli were smaller than those produced by unattended, irrelevant stimuli. Attentional modulations of gamma oscillations in LO and the fusiform gyrus were thus very different, both in their time-course (preparatory period and/or stimulus processing) and direction of modulation (increase or decrease). Our results thus suggest that the functional role of gamma oscillations depends on the area in which they occur.     

Cortical connections of area V4 in the macaque

To determine the locus, full extent, and topographic organization of cortical connections of area V4 (visual area 4), we injected anterograde and retrograde tracers under electrophysiological guidance into 21 sites in 9 macaques. Injection sites included representations ranging from central to far peripheral eccentricities in the upper and lower fields. Our results indicated that all parts of V4 are connected with occipital areas V2 (visual area 2), V3 (visual area 3), and V3A (visual complex V3, part A), superior temporal areas V4t (V4 transition zone), MT (medial temporal area), and FST (fundus of the superior temporal sulcus [STS] area), inferior temporal areas TEO (cytoarchitectonic area TEO in posterior inferior temporal cortex) and TE (cytoarchitectonic area TE in anterior temporal cortex), and the frontal eye field (FEF). By contrast, mainly peripheral field representations of V4 are connected with occipitoparietal areas DP (dorsal prelunate area), VIP (ventral intraparietal area), LIP (lateral intraparietal area), PIP (posterior intraparietal area), parieto-occipital area, and MST (medial STS area), and parahippocampal area TF (cytoarchitectonic area TF on the parahippocampal gyrus). Based on the distribution of labeled cells and terminals, projections from V4 to V2 and V3 are feedback, those to V3A, V4t, MT, DP, VIP, PIP, and FEF are the intermediate type, and those to FST, MST, LIP, TEO, TE, and TF are feedforward. Peripheral field projections from V4 to parietal areas could provide a direct route for rapid activation of circuits serving spatial vision and spatial attention. By contrast, the predominance of central field projections from V4 to inferior temporal areas is consistent with the need for detailed form analysis for object vision.     

High response reliability of neurons in primary visual cortex (V1) of alert, trained monkeys

The reliability of neuronal responses determines the resources needed to represent the external world and constrains the nature of the neural code. Studies of anesthetized animals have indicated that neuronal responses become progressively more variable as information travels from the retina to the cortex. These results have been interpreted to indicate that perception must be based on pooling across relatively large numbers of cells. However, we find that in alert monkeys, responses in primary visual cortex (V1) are as reliable as the inputs from the retina and the thalamus. Moreover, when the effects of fixational eye movements were minimized, response variability (variance/mean - Fano factor, FF) in all V1 layers was low. When presenting optimal stimuli, the median FF was 0.3. High variability, FF approximately 1, was found only near threshold. Our results suggest that in natural vision, suprathreshold perception can be based on small numbers of optimally stimulated cells.     

Contrasting properties of motor output from the supplementary motor area and primary motor cortex in rhesus macaques

The goal of this study was to assess the motor output capabilities of the forelimb representation of the supplementary motor area (SMA) in terms of the sign, latency and strength of effects on electromyographic (EMG) activity. Stimulus triggered averages of EMG activity from 24 muscles of the forelimb were computed in SMA during a reach-to-grasp task. Poststimulus facilitation (PStF) from SMA had two distinct peaks (15.2 and 55.2 ms) and one poststimulus suppression (PStS) peak (32.4 ms). The short onset latency PStF and PStS of SMA were 5.5 and 16.8 ms longer than those of the primary motor cortex (M1). The average magnitudes (peak increase or decrease above baseline) of the short and long latency PStF and PStS from SMA at 60 microA were 13.8, 11.3 and -11.9% respectively. In comparison, M1 PStF and PStS magnitudes at 15 microA were 50.2 and -23.8%. Extrapolating M1 PStF magnitude to 60 microA yields a mean effect that is nearly 15 times greater than the mean PStF from SMA. Moreover, unlike M1, the facilitation of distal muscles from SMA was not significantly greater than the facilitation of proximal muscles. We conclude that the output from SMA to motoneurons is markedly weaker compared with M1 raising doubts about the role of SMA corticospinal neurons in the direct control of muscle activity.     

The reentry hypothesis: the putative interaction of the frontal eye field, ventrolateral prefrontal cortex, and areas V4, IT for attention and eye movement

Attention is known to play a key role in perception, including action selection, object recognition and memory. Despite findings revealing competitive interactions among cell populations, attention remains difficult to explain. The central purpose of this paper is to link up a large number of findings in a single computational approach. Our simulation results suggest that attention can be well explained on a network level involving many areas of the brain. We argue that attention is an emergent phenomenon that arises from reentry and competitive interactions. We hypothesize that guided visual search requires the usage of an object-specific template in prefrontal cortex to sensitize V4 and IT cells whose preferred stimuli match the target template. This induces a feature-specific bias and provides guidance for eye movements. Prior to an eye movement, a spatially organized reentry from occulomotor centers, specifically the movement cells of the frontal eye field, occurs and modulates the gain of V4 and IT cells. The processes involved are elucidated by quantitatively comparing the time course of simulated neural activity with experimental data. Using visual search tasks as an example, we provide clear and empirically testable predictions for the participation of IT, V4 and the frontal eye field in attention. Finally, we explain a possible physiological mechanism that can lead to non-flat search slopes as the result of a slow, parallel discrimination process.     

A comparative study of shape representation in macaque visual areas v2 and v4

We compared aspects of shape representation in extrastriate visual areas V2 and V4, which are both implicated in shape processing and belong to different hierarchical levels. We recorded responses of cells in awake, fixating monkeys to matched sets of contour and grating stimuli of low or intermediate complexity. These included simple stimuli (bars and sinusoids) and more complex stimuli (angles, intersections, arcs, and non-Cartesian gratings), all scaled to receptive field size. The responses of cells within each area were substantially modulated by each shape characteristic tested, with substantial overlap between areas by many response measures. Our analyses revealed many clear and reliable differences between areas in terms of the effectiveness of, and response modulation by, various shape characteristics. Grating stimuli were on average more effective than contour stimuli in V2 and V4, but the difference was more pronounced in V4. As a population, V4 showed greater response modulation by some shape characteristics (including simple shape characteristics) and V2 showed greater response modulation by many others (including complex shape characteristics). Recordings from area V1 demonstrated complex shape selectivity in some cells and relatively modest population differences in comparison with V2. Altogether, the representation of 2-dimensional shape characteristics revealed by this analysis varies substantially among the 3 areas. But surprisingly, the differences revealed by our analyses, individually or collectively, do not parallel the stepwise organization of the anatomical hierarchy. Commonalities of visual shape representation across hierarchical levels may reflect the replication of neural circuits used in generating complex shape representations at multiple spatial scales.     

Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-saporin-induced lesions of the medial prefrontal cortex

Lesions of the basal forebrain (BF) cortical cholinergic system impair performance on a rodent five-choice visual attentional task. This study examines the effects on the same task of selective depletion of acetylcholine from the prefrontal cortex (PFC) using 192 IgG-saporin, the cholinergic immunotoxin. Rats were trained to detect brief visual stimuli, either presented unpredictably both temporally and spatially to increase attentional load, or under less demanding conditions where stimuli were temporally and spatially predictable. Following training, 192 IgG-saporin (50 ng or 100 ng/infusion) or its vehicle was infused bilaterally into the ventromedial PFC. The 100 ng lesion group exhibited post-operatively a transient increase in perseveration, specifically when the visual stimuli were temporally unpredictable. A vigilance decrement, as well as a reinstatement of perseverative responding occurred in both lesion groups under conditions of enhanced attentional load, specifically with high target frequency sustained over many trials. Lesioned subjects were also more impulsive with increased anticipatory errors. Systemic administration of the muscarinic receptor antagonist scopolamine further dissociated the groups with attentional accuracy in the 100 ng group decreasing relative to shams. These findings are consistent with an important modulatory influence of PFC function by BF cholinergic neurons, particularly during increased attentional demand.     

Modulation of NMDA receptor current in layer V pyramidal neurons of the rat prefrontal cortex by P2Y receptor activation

Current responses to N-methyl-D-aspartate (NMDA) in layer V pyramidal neurons of the rat prefrontal cortex were potentiated by the P2 receptor agonists adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP). The failure of these nucleotides to induce inward current on fast local superfusion suggested the activation of P2Y rather than P2X receptors. The potentiation by ATP persisted in a Ca(2+)-free superfusion medium but was abolished by 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl) ester, cyclopiazonic acid, 7-nitroindazole, fluoroacetic acid, bafilomycin, and tetanus toxin, indicating that an astrocytic signaling molecule may participate. Because the metabotropic glutamate receptor (mGluR) agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) (group I/II) and (RS)-3,5-dihydroxyphenylglycine (group I) both imitated the effect of ATP and the group I mGluR antagonist 1-aminoindan-1,5-dicarboxylic acid or a combination of selective mGluR(1) (7-(hydroxyimino)-cyclopropa[b]chromen-1a-carboxylate) and mGluR(5) (2-methyl-6-(phenylethynyl)pyridine) antagonists abolished the facilitation by ATP, it was concluded that the signaling molecule may be glutamate. Pharmacological tools known to interfere with the transduction cascade of type I mGluRs (guanosine 5'-O-(3-thiodiphosphate), U-73122, xestospongin C, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, calmodulin kinase II [CAMKII] inhibitor peptide) depressed the actions of both ATP and ACPD. Characterization of the P2Y receptor by agonists (ATP and UTP), antagonists (suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid), and knockout mice (P2Y(2)(-/-)) suggested that the nucleotides act at the P2Y(4) subtype. In conclusion, we propose that exogenous and probably also endogenous ATP release vesicular glutamate from astrocytes by P2Y(4) receptor activation. This glutamate then stimulates type I mGluRs of layer V pyramidal neurons and via the G(q)/phospholipase C/inositol 1,4,5-trisphosphate/Ca(2+)/CAMKII transduction pathway facilitates NMDA receptor currents.     

在体膜片钳技术比较戊巴比妥钠和乌拉坦麻醉下初级体感皮质神经元的自发膜电位特性

目的 采用在体穿孔全细胞膜片钳技术,记录成年大鼠单个初级体感皮质(S1)神经元,比较戊巴比妥钠和乌拉坦麻醉下神经元的自发膜电位活动. 方法 成年雄性SD大鼠20只,通过腹腔注射戊巴比妥钠或乌拉坦进行麻醉,按麻醉注射药物不同分为戊巴比妥麻醉组和乌拉坦麻醉组(每组10只),将头部固定于立体定位仪上,待麻醉稳定后进行在体穿孔膜片钳记录. 结果 实验在戊巴比妥钠组和乌拉坦麻醉组中各记录了27个S1神经元.结果显示:戊巴比妥麻醉组和乌拉坦麻醉组神经元的静息膜电位[(-84±4)mV比(-82±4)mV,P＞0.05]、动作电位发放频率[(0.28±0.28) Hz比(0.33±0.34) Hz,P＞0.05]和动作电位幅度[(58±10) mV比(63±8) mV,P＞0.05]比较,差异均没有统计学意义;但是两种麻醉药物作用下,神经元的自发膜电位变化模式完全不同,戊巴比妥钠麻醉下只包括短的兴奋性突触后电位,膜电位的累计分布呈单峰,而乌拉坦麻醉下呈现去极化(UP)和超极化(DOWN)交替出现的膜电位振荡,且膜电位的累计分布呈明显的双峰. 结论 在戊巴比妥钠和乌拉坦作用下,初级体感皮质神经元的膜电位变化模式不同.     

Bursting of prefrontal cortex neurons in awake rats is regulated by metabotropic glutamate 5 (mGlu5) receptors: rate-dependent influence and interaction with NMDA receptors

Metabotropic glutamate 5 (mGlu5) receptors have been recently implicated in prefrontal cortex (PFC)-dependent executive functions because inhibition of mGlu5 receptors impairs working memory and worsens cognitive-impairing effects of NMDA receptor antagonists. To better understand the mechanisms by which mGlu5 receptors influence PFC function, we examined the effects of selective mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), given alone or in combination with the NMDA receptor antagonist MK801, on ensemble single unit activity in the medial PFC (mPFC) of behaving rats. MPEP decreased the spontaneous burst activity of the majority of mPFC neurons. This inhibition was selective for the most active cells because greater decreases were observed in neurons with higher baseline firing rates. MPEP augmented the effects of MK801 on burst activity, variability of spike firing and random spike activity. These findings demonstrate that in awake animals mGlu5 receptors regulate the function of PFC neurons by two related mechanisms: (i) rate-dependent excitatory influence on spontaneous burst activity; and (ii) potentiation of NMDA receptor mediated effects on firing rate and burst activity. These mechanisms support the idea that modulation of mGlu5 receptors may provide a pharmacological strategy for fine-tuning the temporal pattern of firing of PFC neurons.     

Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe stimulation in vivo: involvement of serotonin and GABA

Serotonin is involved in psychiatric disorders exhibiting abnormal prefrontal cortex (PFC) function (e.g. major depression, schizophrenia). We examined the effect of the stimulation of the dorsal and median raphe nuclei (DR and MnR, respectively) on the activity of PFC neurons. Electrical stimulation of DR/MnR inhibited 66% (115/173) of pyramidal neurons in the medial PFC (mPFC). The rest of the cases exhibited orthodromic excitations, either pure (13%) or preceded by short-latency inhibitions (20%). Excited neurons had a lower pre-stimulus firing rate than those inhibited. Excitations evoked by MnR stimulation had a shorter latency than those evoked by DR stimulation. WAY-100635 [a 5-hydroxytryptamine1A (5-HT1A) antagonist] and the selective gamma aminobutyric acidA (GABAA) antagonist picrotoxinin partially antagonized DR/MnR-evoked inhibitions, suggesting the involvement of 5-HT1A- and GABAA-mediated components. The presence of a direct DR/MnR-mPFC GABAergic component is suggested by the short latency of evoked inhibitions (9 +/- 1 ms), faster than those evoked in the secondary motor area (20 +/- 3 ms), and that of antidromic spikes evoked by DR/MnR stimulation in mPFC pyramidal neurons (15 +/- 1 ms). Stimulation of the DR/MnR with paired pulses enhanced the duration of inhibitions and turned some excitations into inhibitions. Thus, the DR/MnR control the activity of mPFC pyramidal neurons in vivo in a complex manner, involving 5-HT-mediated excitations and GABA- and 5-HT-mediated inhibitions.     

Effect of partial cystectomy on the induction of pre-neoplastic lesions in rat bladder initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine followed by bladder carcinogens and promoters

Summary The effect of partial cystectomy on the occurrence of pre-neoplastic lesions, papillary or nodular hyperplasia (PN hyperplasia), of the bladder in male F344 rats was studied in an experiment in which bladder carcinogens and promoters were given to the rats after initiation with BBN. The bladder carcinogens tested were N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) and N-4[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and the bladder promoters were sodium saccharin, sodium cyclamate, and DL-tryptophan. Partial cystectomy significantly decreased the occurrence of PN hyperplasia in rats treated with EHBN and tended to inhibit that in rats given saccharin or tryptophan. Thus partial cystectomy inhibited rather than enhanced the induction of PN hyperplasia.