Spatial phase sensitivity of V1 neurons in alert monkey

The activity of V1 neurons evoked by stimuli within the classical receptive field (CRF) is known to be modulated by stimuli in the surrounding field, the extra-receptive field (ERF). By varying the relative spatial phase (RSP) between a central grating presented in the CRF and a surround grating in the ERF, we studied the contextual modulation in V1 neurons of alert monkeys (Macaca mulata). Results from two monkeys show that most of the V1 neurons with suppressive ERF are sensitive to the RSP, and the degree of sensitivity is strongly dependent on the strength of ERF suppression. This sensitivity is maximal when the RSP is generated at or near CRF/ERF boundary, but is observed over the entire ERF. Interestingly, the suppressive effect of the surround grating can be largely abolished by inserting a narrow gap between the center and surround gratings or by a phase displacement between them corresponding to <10% of the CRF diameter. These properties of V1 neurons may serve important perceptual functions.     

Impaired filtering of distracter stimuli by TE neurons following V4 and TEO lesions in macaques

Directing attention to a behaviorally relevant visual stimulus can overcome the distracting effects of other nearby stimuli. Correspondingly, physiological studies indicate that attention serves to filter distracting stimuli from receptive fields (RFs) in several extrastriate areas. Moreover, a recent study demonstrated that lesions of extrastriate areas V4 and TEO produce impairments in attentional filtering. A critical remaining question concerns why lesions of ventral stream areas cause attentional filtering impairments. To address this question, we tested the effects of restricted area V4 and TEO lesions on both behavioral performance and the responses of downstream neurons in area TE. The lesions impaired behavioral discrimination thresholds and altered neuronal selectivity for target stimuli in the presence of distracters. With attention to the target, but in the absence of V4 and/or TEO inputs, TE neurons responded as though attentional inputs could no longer be used to filter distracters from their RFs. This presumably occurred because top-down attentional signals were no longer able to filter distracters from the RFs of the cells that provide TE with major input. Consistent with this interpretation, increasing the spatial separation between targets and distracters, such that they no longer fell within a typical V4 RF dimension, restored both behavioral performance and neuronal selectivity in the portion of TE RFs affected by the V4 lesion.     

The current status of the New World monkey phylogeny

Four DNA datasets were combined in tandem (6700 bp) and Maximum parsimony and Neighbor-Joining analyses were performed. The results suggest three groups emerging almost at the same time: Atelidae, Pitheciidae and Cebidae. The total analysis strongly supports the monophyly of the Cebidae family, grouping Aotus, Cebus and Saimiri with the small callitrichines. In the callitrichines, the data link Cebuela to Callithrix, place Callimico as a sister group of Callithrix/Cebuella, and show Saguinus to be the earliest offshoot of the callitrichines. In the family Pithecidae, Callicebus is the basal genus. Finally, combined molecular data showed congruent branching in the atelid clade, setting up Alouatta as the basal lineage and Brachyteles-Lagothrix as a sister group and the most derived branch. Two major points remain to be clarified in the platyrrhine phylogeny: (i) what is the exact branching pattern of Aotus, Cebus, Saimiri and the small callitrichines, and (ii), which two of these three lineages, pitheciines, atelines or cebids, are more closely related?     

Functional organization of color domains in V1 and V2 of macaque monkey revealed by optical imaging

Areas V1 and V2 of Macaque monkey visual cortex are characterized by unique cytochrome-oxidase (CO)-staining patterns. Initial electrophysiological studies associated CO blobs in V1 with processing of surface properties such as color and brightness and the interblobs with contour information processing. However, many subsequent studies showed controversial results, some supporting this proposal and others failing to find significant functional differences between blobs and interblobs. In this study, we have used optical imaging to map color-selective responses in V1 and V2. In V1, we find striking "blob-like" patterns of color response. Fine alignment of optical maps and CO-stained tissue revealed that color domains in V1 strongly associate with CO blobs. We also find color domains in V1 align along centers of ocular dominance columns. Furthermore, color blobs in V1 have low orientation selectivity and do not overlap with centers of orientation domains. In V2, color domains coincide with thin stripes; orientation-selective domains coincide with thick and pale stripes. We conclude that color and orientation-selective responses are preferentially located in distinct CO compartments in V1 and V2. We propose that the term "blob" encompasses both the concept of "CO blob" and "color domain" in V1.     

Optical imaging of contrast response in Macaque monkey V1 and V2

Our studies on brightness information processing in Macaque monkey visual cortex suggest that the thin stripes in the secondary visual area (V2) are preferentially activated by brightness stimuli (such as full field luminance modulation and illusory edge-induced brightness modulation). To further examine this possibility, we used intrinsic signal optical imaging to examine contrast response of different functional domains in primary and secondary visual areas (V1 and V2). Color and orientation stimuli were used to map functional domains in V1 (color domains, orientation domains) and V2 (thin stripes, thick/pale stripes). To examine contrast response, sinusoidal gratings at different contrasts and spatial frequencies were presented. We find that, consistent with previous studies, the optical signal increased systematically with contrast level. Unlike single-unit responses, optical signals for both color domains and orientation domains in V1 exhibit linear contrast response functions, thereby providing a large dynamic range for V1 contrast response. In contrast to domains in V1, domains in V2 exhibit nonlinear responses, characterized by high gain at low contrasts, saturating at a mid-high contrast levels. At high contrasts, thin stripes exhibit increasing response, whereas thick/pale stripes saturate, consistent with a strong parvocellular input to thin stripes. These findings suggest that, with respect to contrast encoding, thin stripes have a larger dynamic range than thick/pale stripes and further support a role for thin stripes in processing of brightness information.     

Effect of systemic morphine on the responses of convergent neurons to noxious heat stimuli applied over graded surface areas

BACKGROUND: Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord. METHODS: Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2). RESULTS: The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11+/-4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159+/-36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42+/-24% of control values; P < 0.05) than was observed with the smaller stimulus. CONCLUSIONS: Doses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated. Such effects are difficult to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid-induced depression of descending inhibitory influences triggered by spatial summation.     

Laminar distribution of neurons projecting from area V1 to V2 in macaque and squirrel monkeys.

The present study reevaluates the sublaminar distribution and cellular morphology of neurons projecting from area V1 to V2. Observations are based on retrogradely transported HRP, Phaseolus vulgaris leucoagglutinin (PHA-L), or biocytin after injections made in area V2 of three squirrel monkeys and eight macaques. With material prepared in the coronal or horizontal tissue planes, it is clear that projection neurons in V1, in both species, are concentrated in layer 4B and in a single band (150-250 microns wide) restricted to the upper subdivision of layer 3 (layer 3A). There are also labeled neurons, but fewer in number, in layers 3B and 4A, and occasionally in layers 2 and 5. Golgi-like labeling from PHA-L or biocytin confirmed that most of the projection neurons in layer 3A are pyramidal. As reported for several other corticocortical systems, these pyramidal neurons differ in soma size, soma shape, and dendritic geometry. These results emphasize the complex organization of layer 3, and the distributed nature of efferent projections from area V1. Given the selective connectivity of vertical interlaminar networks, these results specifically suggest that information transmitted to area V2 from neurons in layer 3A reflects more highly processed, convergent input than that originating from either layer 3B or 4B.     

Visual motion responses in the posterior cingulate sulcus: a comparison to V5/MT and MST

Motion processing regions apart from V5+/MT+ are still relatively poorly understood. Here, we used functional magnetic resonance imaging to perform a detailed functional analysis of the recently described cingulate sulcus visual area (CSv) in the dorsal posterior cingulate cortex. We used distinct types of visual motion stimuli to compare CSv with V5/MT and MST, including a visual pursuit paradigm. Both V5/MT and MST preferred 3D flow over 2D planar motion, responded less yet substantially to random motion, had a strong preference for contralateral versus ipsilateral stimulation, and responded nearly equally to contralateral and to full-field stimuli. In contrast, CSv had a pronounced preference to 2D planar motion over 3D flow, did not respond to random motion, had a weak and nonsignificant lateralization that was significantly smaller than that of MST, and strongly preferred full-field over contralateral stimuli. In addition, CSv had a better capability to integrate eye movements with retinal motion compared with V5/MT and MST. CSv thus differs from V5+/MT+ by its unique preference to full-field, coherent, and planar motion cues. These results place CSv in a good position to process visual cues related to self-induced motion, in particular those associated to eye or lateral head movements.     

Distribution of non-phosphorylated neurofilament in squirrel monkey V1 is complementary to the pattern of cytochrome-oxidase blobs

The geniculo-recipient zones of the primate primary visual cortex (V1) stain more strongly for cytochrome oxidase (CO) than other regions. Labeling V1 with an antibody (SMI-32) against neurofilament protein produces a laminar pattern that is largely complementary to that of CO: the layers that receive the strongest geniculate input react weakly for SMI-32. We evaluated whether the complementary laminar relationship extends throughout the superficial layers where there are regularly spaced blobs of dark CO staining that are known to receive geniculate input. In all hemispheres, neurofilament labeling in the superficial layers was indeed complementary to the CO pattern. The density of SMI-32 labeled neurons was quantified and found to be greater within the CO interblobs than in the blobs. These results demonstrate that blobs and interblobs can be distinguished by examining the pattern of neurofilament expression in V1. That neurofilament expression is highest within interblobs raises the possibility that the distribution of cell types may be non-uniform across blobs and interblobs.     

Differentiating heavy from light drinkers by neural responses to visual alcohol cues and other motivational stimuli

The course to alcohol dependence often starts with a preclinical period of heavy drinking. The present article reports functional magnetic resonance imaging data showing that even this pattern of alcohol consumption is associated with maladaptive neural responses to alcohol and other stimuli. When participants were confronted with visual cues related to alcohol, heavy drinkers showed amplified blood oxygen level-dependent signal responses in specific emotional areas (insular cortex) and in parts of the brain's reward circuitry (ventral striatum). This neuronal amplification was not present in light drinkers. Crucially, at the same time heavy drinkers showed reduced responses in frontal areas to pictures related to higher order life goals and in the cingulate cortex to appetitive food stimuli, suggesting that they have difficulty finding alternative, socially desirable goals. Using discriminant function analysis, we demonstrate that the combination of alcohol-related overactivation and underactivation to alternative goals allows heavy and light drinkers to be differentiated with a high degree of precision. Our findings highlight the diagnostic value of functional brain mapping of cue reactivity. Imaging measures may help to identify addictive dispositions in preclinical stages and to clarify the mechanisms that underlie the development and maintenance of alcohol dependence.     

Enhanced response of neurons in rat somatosensory cortex to stimuli containing temporal noise

Sensory stimuli under natural conditions often consist of a temporally irregular sequence of events, contrasting with the periodic sequences commonly used as stimuli in the laboratory. These experiments compared the responses of neurons in rat barrel cortex with trains of whisker movements with different frequencies; each train possessed either a periodic or an irregular, "noisy" temporal structure. Periodic stimulus trains were composed of a sequence of 21 whisker deflections separated by 20 equal interdeflection intervals (IDIs). Noisy trains were matched for mean IDI but included intervals shorter and longer than the mean IDI. Cortical responses were equivalent for periodic and noisy stimuli for frequencies up to 10 Hz. Above 10 Hz, temporal noise led to a larger response magnitude, and this effect was amplified as deflection frequency increased. Noise also caused a sharpening of the temporal precision of response to the individual deflections of the stimulus train. Cortical neurons thus appear to be "tuned" to respond in a different way to stimuli characterized by temporal unpredictability. As a consequence, perceptual judgments that depend on somatosensory cortical firing rate may be affected by the presence of temporal noise.     

Modulation of responses to optic flow in area 7a by retinotopic and oculomotor cues in monkey

Perception of two- and three-dimensional optic flow critically depends upon extrastriate cortices that are part of the 'dorsal stream' for visual processing. Neurons in area 7a, a sub-region of the posterior parietal cortex, have a dual sensitivity to visual input and to eye position. The sensitivity and selectivity of area 7a neurons to three sensory cues - optic flow, retinotopic stimulus position and eye position - were studied. The visual response to optic flow was modulated by the retinotopic stimulus position and by the eye position in the orbit. The position dependence of the retinal and eye position modulation (i.e. gain field) were quantified by a quadratic regression model that allowed for linear or peaked receptive fields. A local maximum (or minimum) in both the retinotopic fields and the gain fields was observed, suggesting that these sensory qualities are not necessarily linearly represented in area 7a. Neurons were also found that simply encoded the eye position in the absence of optic flow. The spatial tuning for the eye position signals upon stationary stimuli and optic flow was not the same, suggesting multiple anatomical sources of the signals. These neurons can provide a substrate for spatial representation while primates move in the environment.      

Neurokinin-1 receptors are involved in behavioral responses to high-intensity heat stimuli and capsaicin-induced hyperalgesia in mice.

BACKGROUND: The neurokinin-1 (NK-1) receptor and its ligand, substance P, are thought to play important roles in nociception and hyperalgesia. This study evaluated the role of the NK-1 receptor in processing noxious stimuli in normal and inflammatory states. METHODS: Behavioral responses to heat and mechanical and chemical stimuli were studied in NK-1 receptor knockout mice and wild-type control mice. Thermal nociception was evaluated by measuring paw lick or jump latencies to hot plate (52, 55, and 58 degrees C) and paw withdrawal latencies to radiant heat applied to the hind paws. Mechanical nociception was measured by von Frey monofilament applications to the hind paws. Intraplantar capsaicin-induced (10 microg/20 microl) paw licking and mechanical and heat hyperalgesia were compared in NK-1 knockout and wild-type mice. RESULTS: Withdrawal responses to radiant heat (4.3+/-0.18 s for knockout and 4.4+/-0.8 s for wild-type mice) and von Frey monofilaments were similar in knockout and wild-type mice. In the hot plate test, increasing the hot plate temperature from 52 degrees C to 58 degrees C resulted in a decrease in the response latency in the wild-type mice (30.4+/-17.5 s to 15.2+/-6.8 s, P < 0.05), whereas in the knockout mice the response latencies remained constant (28.2+/-19.8 s to 29+/-15.1 s, not significant). Capsaicin-induced paw licking (14.5+/-12.8 s for knockout and 41.3+/-37.3 s for wild-type mice, P < 0.05) and mechanical and heat hyperalgesia were attenuated in the knockout mice. CONCLUSION: NK-1 receptors contribute to the withdrawal responses to high-intensity heat stimuli and to capsaicin-induced mechanical and heat hyperalgesia.     

Selective activation of medial prefrontal-to-accumbens projection neurons by amygdala stimulation and Pavlovian conditioned stimuli

Medial prefrontal cortex (mPFC) neurons respond to Pavlovian conditioned stimuli, and these responses depend on input from the basolateral amygdala (BLA). In this study, we examined the mPFC efferent circuits mediating conditioned responding by testing whether specific subsets of mPFC projection neurons receive BLA input and respond to conditioned stimuli. In urethane-anesthetized rats, we identified mPFC neurons that projected to the nucleus accumbens (NAcc) or to the contralateral mPFC (cmPFC) using antidromic activation. Stimulation of the BLA and Pavlovian conditioned odors selectively activated a subpopulation of ventral mPFC neurons that projected to NAcc, but elicited virtually no activation in mPFC neurons that projected to cmPFC. BLA stimulation typically evoked inhibitory responses among nonactivated neurons projecting to either site. These results suggest that the ventral mPFC-to-NAcc pathway may support behavioral responses to conditioned cues. Furthermore, because projections from the BLA (which also encode affective information) and the mPFC converge within the NAcc, the BLA may recruit the mPFC to drive specific sets of NAcc neurons, and thereby exert control over prefrontal cortical-striato-thalamocortical information flow.     

Contribution of GABAergic inhibition to receptive field structures of monkey inferior temporal neurons.

Receptive field (RF) structures of neurons in area TE of the monkey inferior temporal cortex were investigated under blockade of inhibition mediated by gamma-aminobutyric acid (GABA). Bicuculline methiodide, a GABA(A) receptor antagonist, was microiontophoretically administered to TE neurons. Blockade of inhibition enhanced responses to a particular range of visual stimuli not only at the RF center, but also at the periphery of or outside RFs where the stimuli originally evoked little or no response, enlarging the RFs. The strongest responses under normal and uninhibited conditions occurred at the RF center in most neurons. The largest increase in responses, reflecting the strongest inhibitory input, usually occurred at the RF center, but in some neurons it occurred in the periphery. A neuron had a silent region within its RF where some stimuli effective at adjacent locations could not elicit responses even under blockade of inhibition. We suggest that (i) afferent information to individual TE neurons originates from a wide retinotopic region beyond their normal RF; (ii) the afferent convergence is not necessarily complete throughout a RF; and (iii) GABAergic inhibition contributes to the generation of RF structures of TE neurons.     

Segregation and convergence of functionally defined V2 thin stripe and interstripe compartment projections to area V4 of macaques

The organization of projections from V2 thin stripes and interstripes to V4 was investigated using a combination of physiological and anatomical techniques. The compartments of V2 were first characterized, in vivo, using optical recording of intrinsic signals. Multiple anterograde tracers were then injected into different V2 compartments. The distribution of labeled axons was analyzed in tangential or horizontal sections including V4. A small iontophoretic injection, either in a thin stripe or an interstripe, labeled a large primary and several secondary foci in V4. The primary foci from the thin stripe and interstripe were spatially segregated by a gap of approximately 1 mm. Furthermore, less dense regions within the primary foci were often 'filled-in' by secondary foci from the opposite V2 compartment. When two injections were made both at interstripes, their projections to V4 were almost entirely overlapping. These anatomical patterns indicate that segregation and convergence of intercortical pathways are both important features of V4 organization. Furthermore, the size of cortical modules increases considerably from the blobs of V1, through the stripes of V2, to the afferent domains of V4.     

Nociceptive responses to chronic stress of restraint and noxious stimuli in sucrose fed rats

Stress produces analgesia and sucrose ingestion immediately relieves the stress in both the rat and human models, however the effect of sucrose feeding on chronic stress of repeated varying pain is not known. Adult male rats were subjected to a stress regimen of restraint and various degrees of noxious stimuli given repeatedly during 58 h in six sessions with a rest of 32 h. In a 4‐h session, the rats were subjected to the stress of thermal noxious stimulation, pin prick and electrical stimulation of nociceptive afferents (six, one and nine times at intervals of 5 min) in addition to the restraint stress. The effect of this stress on their nociceptive responses was noted as hind paw lick latency, HPL; tail flick latency, TFL; threshold of tail flick, TF; vocalization during stimulus, SV and vocalization after discharge, VA. On the fourth day, the rats received sucrose solution (20 percent orally) ad libitum, which was withdrawn after session IV. During session II–IV in pre‐sucrose fed state, the TFL remained unaffected as compared to session I, while the HPL decreased (18.53 ± 4.96 s, 12.01 ± 4.64 s in sessions I, VI respectively); and the thresholds for TF, SV and VA (0.34 ± 0.16 and 0.71 ± 0.32 mA in session I, VI respectively) progressively increased. After sucrose ingestion during sessions II–IV, the above‐mentioned decrease in HPL and increase in thresholds was not observed. However, they appeared after discontinuation of sucrose during sessions V and VI. The results of our experiment suggest that exposure to our novel model of chronic (58 h) albeit intermittent stress of noxious stimuli and restraint produced an analgesic response in the threshold of TF, SV and VA, an hyperalgesic response in HPL and no effect in TFL; which were attenuated by ingesting a palatable sucrose solution ad libitum. Copyright © 2001 John Wiley & Sons, Ltd.     

Effects of ketamine on behavioral responses to somatic and visceral stimuli in rats]

The responses to colorectal distension as a visceral stimulus were observed and tail-flick test was performed in rats, after intraperitoneal administration of ketamine 30 mg.kg-1 (n = 6) or 100 mg.kg-1 (n = 5). After determining control colorectal distension and tail-flick values, both procedures were repeated every 10 minutes for one hour in both groups. The control thresholds for colorectal distension and tail-flick latencies were 20.8 +/- 1.0 mmHg and 4.5 +/- 0.3 sec (mean +/- SD), respectively in ketamine 30 mg.kg-1 group. They were 21.2 +/- 1.1 mmHg and 4.7 +/- 0.4 sec in ketamine 100 mg.kg-1 group. These baseline threshold and latency values in the two groups were not significantly different. Ten minutes after ketamine administration, the colorectal distension thresholds and tail-flick latencies were 43.7 +/- 7.2 mmHg and 6.4 +/- 0.9 sec, respectively in ketamine 30 mg.kg-1 group. They were 53.3 +/- 14.8 mmHg and 7.2 +/- 0.8 sec, respectively in ketamine 100 mg.kg-1 group. These values were significantly greater than the preketamine control values in both groups. The present study demonstrates that ketamine exerts apparent analgesic effects against both visceral and somatic stimuli. These results led us to consider that ketamine may be clinically useful to control visceral pain.     

Effects of cholinergic modulation on responses of neocortical neurons to fluctuating input

Neocortical neurons in vivo are spontaneously active and intracellular recordings have revealed strongly fluctuating membrane potentials arising from the irregular arrival of excitatory and inhibitory synaptic potentials. In addition to these rapid fluctuations, more slowly varying influences from diffuse activation of neuromodulatory systems alter the excitability of cortical neurons by modulating a variety of potassium conductances. In particular, acetylcholine, which effects learning and memory, reduces the slow alterhyperpolarization, which contributes to spike frequency adaptation. We used whole-cell patch-clamp recordings of pyramidal neurons in neocortical slices and computational simulations to show, first, that when fluctuating inputs were added to a constant current pulse, spike frequency adaptation was reduced as the amplitude of the fluctuations was increased. High- frequency, high-amplitude fluctuating inputs that resembled in vivo conditions exhibited only weak spike frequency adaptation. Second, bath application of carbachol, a cholinergic agonist, significantly increased the firing rate in response to a fluctuating input but minimally displaced the spike times by < 3 ms, comparable to the spike jitter observed when a visual stimulus is repeated under in vivo conditions. These results suggest that cholinergic modulation may preserve information encoded in precise spike timing, but not in interspike intervals, and that cholinergic mechanisms other than those involving adaptation may contribute significantly to cholinergic modulation of learning and memory.