Responses of striatal neurons in the behaving monkey. 1. Head of the caudate nucleus

The activity of 394 neurons in the head of the caudate nucleus and the most anterior part of the putamen was analyzed in 3 behaving rhesus monkeys in order to analyze the functions of this part of the striatum. Of these neurons, 64.2% responded in the tests used in relation to, for example, environmental events, movements made by the monkey, the performance of a visual discrimination, or during feeding. However, only relatively small proportions of these neurons had responses which were unconditionally related to visual (9.6%), auditory (3.5%), or gustatory (0.5%) stimuli, or to movements (4.1%). Instead, the majority of the responsive neurons had activity in relation to stimuli or movements which was conditional, in that the responses occurred in only some test situations, and were often dependent on the performance of a task by the monkeys. Thus, it was found in the visual discrimination task that 14.5% of the neurons responded during a 0.5 sec tone/light cue period which signalled the start of each trial; 31.1% responded in the period in which the discriminative visual stimuli were shown, with 24.3% of these responding more to either the visual stimulus which signified food reward or to that which signified punishment; and 6.2% responded in relation to lick responses. Yet these neurons typically did not respond in relation to the cue stimuli, to the visual stimuli, or to movements, when these occurred independently of the task, or when performance of the task was prevented. Comparably, of the neurons tested during feeding, 25.8% responded when the food was seen by the monkey, 6.2% when he tasted it, and 22.4% during a cue given by the experimenter that a food or non-food object was about to be presented. However, only few of these neurons had responses to the same stimuli presented in different situations.It is concluded that many neurons in the head of the caudate nucleus and the most anterior part of the putamen respond in relation to events which are used as cues to prepare for the performance of tasks, including feeding, in which movements must be initiated. Other neurons respond in relation to the stimuli used and the movements made in these tasks. However, the majority of these neurons do not have unconditional sensory or motor responses. It is therefore suggested that the anterior neostriatum contains neuronal mechanisms which are important in the process by which environmental cues are used in the preparation of behavioral responses, and in the initiation of particular behavioral responses made in particular situations to particular environmental stimuli. Deficits in the initiation of movements following damage to striatal pathways may arise in part because of interference with these functions of the anterior neostriatum.     

Visual responses of neurons in the dorsolateral amygdala of the alert monkey

There is evidence that the inferotemporal visual cortex in the monkey projects to the amygdala, and evidence that damage to this region impairs the learning of associations between visual stimuli and reward or punishment. In recordings made in the amygdala to determine whether or not visual responses were found, and if so how they were affected by the significance of the visual stimuli, neurons were found in the dorsolateral part of the amygdala with visual responses which in most cases were sustained while the animal looked at effective visual stimuli. The latency of the responses was 100 to 140 ms or more. The majority (85%) of these neurons responded more strongly to some stimuli than to others, but physical factors which accounted for the responses of the neurons, such as shape, size, orientation, color, or texture, could not usually be identified. Although 22 (19.5%) of these neurons responded primarily to food objects, the responses were not uniquely food-related. Furthermore, although some neurons responded in a visual discrimination test to a visual stimulus which indicated reward, and not to a visual stimulus which indicated saline, only minor modifications of the magnitude of the neuronal responses to the stimuli were obtained when the reward-related significance of the stimuli was reversed. The visual responses of these amygdaloid neurons were thus intermediate in some respects between those of neurons in the inferotemporal cortex, which are not affected by the significance of visual stimuli, and those of neurons in a region to which the amygdala projects, the lateral hypothalamus and substantia innominata, where neurons respond to visual stimuli associated with food reward.     

Responses of hippocampal formation neurons in the monkey related to delayed spatial response and object-place memory tasks

The memory for where in the environment a particular visual stimulus has been seen is one of the types of memory relatively specifically impaired by hippocampal damage in primates including man. In order to investigate what processing might be performed by the hippocampus related to this type of memory, the activity of hippocampal neurons was recorded while monkeys performed an object-place memory task. In this task, the monkey was shown a sample stimulus in one position on a video screen, there was a delay of 2 s, and then the same or a different stimulus was shown in the same or in a different position. The monkey remembered the sample and its position, and if both matched the delayed stimulus, he licked to obtain fruit juice. Of the 600 neurons analysed in this task, 3.8% responded differently for the different spatial positions, with some of these responding differentially during the sample presentation, some in the delay period, and some in the match period. Thus some hippocampal neurons respond differently for stimuli shown in different positions in space, and some respond differently when the monkey is remembering different positions in space. In addition some of the neurons responded to a combination of object and place information, in that they responded only to a novel object in a particular place. These neuronal responses were not due to any response being made or prepared by the monkey, for information about which behavioral response was required was not available until the match stimulus was shown. This is the first demonstration that some hippocampal neurons in the primate have activity related to the spatial position of stimuli. The activity of these neurons was also measured in a delayed spatial response task, in which the monkey was shown a stimulus in one position, and, after a 2 s delay when two identical stimuli were shown, had to reach to touch the stimulus which was in the position in which it had previously been seen. It was found that the majority of the neurons which responded in the object-place memory task did not respond in the delayed response task. Instead, a different population of neurons (5.7% of the total) responded in the delayed spatial response task, with differential left-right responses in the sample, delay, or match periods.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pathway-specific habituation of induced gamma oscillations in the hippocampal slice

Brief tetanic stimulation (eight pulses at 100 Hz) of afferent fibers innervating area CA1 of the hippocampus produce gamma oscillations. When delivered every minute the oscillation habituated markedly after the first stimulus. This habituation could be transiently reversed by stimulating a different pathway to the recorded area. Gamma oscillation-induced beta frequency oscillations were only seen in response to the first (novel) stimulus and the gamma oscillation itself was markedly attenuated by on-going, non-oscillogenic, synaptic activity. The NMDA receptor antagonist ketamine abolished the response to novel stimuli but left the habituated response relatively unaffected. The pattern of habituation parallelled that seen for sensory induced gamma and beta oscillations in the clinical EEG.     

Topographic distribution of modality-specific amygdalar neurons in alert monkey

Neuronal activity in the amygdala (AM) was recorded from alert monkeys during performance of tasks that led to presentation of rewarding or aversive stimuli. The tasks had 3 phases: (1) discrimination (visual, auditory), (2) operant response (bar pressing), and (3) ingestion (reward) or avoidance (aversion). Neuronal activity was analyzed and compared during each of these phases. Of 585 AM neurons tested, 312 (53.3%) responded to at least one stimulus in one or more of 5 major groups: vision related, audition related, ingestion related, multimodal, and selective. Forty neurons (6.8%) in the anterior dorsolateral capsule of the basolateral nuclei responded exclusively to visual stimuli (vision related). Twenty-six neurons (4.4%) further posterior in the basolateral group responded only to auditory stimuli (audition related). During ingestion an additional 41 neurons (7.0%) increased their activity (ingestion related). These were in the corticomedial group and at the boundaries between the nuclei of the basolateral group. Of these, 27 responded only in the ingestion phase, 11 during ingestion and at the sight of food, and 3 during ingestion and to certain sounds. Throughout the AM other neurons (n = 117, 20.0%) responded to visual, auditory, and somesthetic stimuli and, when tested, to involuntary ingestion of liquid (multimodal). Of these, 40 responded transiently (phasic; 36 excited, 4 inhibited). The remaining 77 maintained their altered activity into the subsequent phases of the task (tonic; 69 excited, 8 inhibited). In each of these 4 categories, most cells were activated primarily by novel or unfamiliar stimuli, and their responses habituated during repeated stimulation. A small number of cells in the basolateral and the basomedial nuclei (n = 14, 2.4%) were highly selective in that they responded specifically to one biologically significant object or sound more than to any other stimuli (selective). Some of these neurons responded to both sight and ingestion of a specific food. In summary, most AM neurons responded vigorously to novel stimuli, and some of the neurons had multimodal responsiveness. These results suggest the AM is related to processing of new environmental stimuli and to those cross-modal association.     

Pattern motion and component motion sensitivity in cat superior colliculus

Single neurons in the superior colliculus of the cat were tested for their direction-tuning responses to random-line patterns composed of identical short lines moving obliquely to their common orientation. A substantial population of cells responded primarily to the veridical direction of pattern motion while a few were sensitive to the orientation of component lines. Moreover, for most cells, the pattern motion sensitivity decreased when the orientation element was enhanced by elongating the component lines in stimulus. Further analysis found that the initial transient responses after stimulus onset were relatively more sensitive to component motion than the subsequent sustained responses. These findings suggest that the superior colliculus is involved in the higher-order analysis of visual motion so that collicular neurons can signal coherent pattern motion in many cases.     

Neuronal activity in the monkey dorsolateral prefrontal cortex during a discrimination task with delay

Ninety-nine single neuron activities of the dorsolateral prefrontal cortex of 3 monkeys were recorded during performance of a Konorski task. Green or red lights were presented successively with a separation of fixed delay interval. The monkey responded as soon as the second stimulus was presented. If the two stimuli were color-matched, the ‘YES’ lever press was rewarded; if the two stimuli were not, the ‘NO’ lever press was rewarded. In the second task, after paired color stimuli, a tone pip was presented as the ‘GO’ signal for lever presses. During sample and matching periods 50 neurons increased their discharge rates and 10 decreased. In 86% of increasing type neurons rate increase occurred during both periods. During auditory GO periods, 27 neurons increased their rates and 11 decreased. Discharge peak was before or at the moment of hold key release. In 60% of these neurons were also observed the rate changes to sample and matching stimuli. Differential activations between left and right levers were found in 20%. It was suggested that the prefrontal cortex is related to a sensorial attention mechanism to the visual stimulus which enables correct choice of the behavior to be rewarded.     

Amygdaloid neuronal responses to complex visual stimuli in an operant feeding situation in the monkey

In chronically prepared monkeys, 337 neurons were recorded from the anterolateral amygdala during an operant task that required visual discrimination. Twelve percent (39/337) of the neurons responded to one or more of food or non-food visual stimuli. A subset of these responsive neurons was selectively sensitive to the sight of non-food objects with aversive associations. Simultaneous presentation of a food stimulus with the aversive object inhibited the response of these neurons. These response characteristics could not be explained by simple sensory processing of the visual stimuli. It is suggested that the amygdala plays an important role in the elaboration of motivational behavior by using the complex or associative properties of visual stimuli.     

Tolerances of responses to visual patterns in neurons of the posterior inferotemporal cortex in the macaque against changing stimulus size and orientation, and deleting patterns

Neuronal activities were recorded in areas TEO and TE of the inferotemporal cortex in four hemispheres of two monkeys during the performance of a visual pattern discrimination task. Tolerances of responses to patterns against changing stimulus size and orientation, and deleting patterns halves were investigated and compared between TEO and TE neurons. Of 311 neurons tested, 80 (26%) responded to one or more patterns out of four standard patterns. Of these 80 neurons, 50 (63%) were recorded in area TEO and 30 (38%) in area TE. Neurons responsive to patterns were recorded in both areas TEO and TE, however degrees of tolerance of responses were different between TEO and TE neurons. Tolerances of TEO neurons were moderate and degrees of tolerance varied from neuron to neuron. Responses to particular patterns were dependent on stimulus size, stimulus orientation, and/or completeness of patterns. By contrast, tolerances of TE neurons were generally strong. Responses to particular patterns were not affected by changing stimulus size, changing stimulus orientation nor deleting patterns halves. These results suggest that area TEO rather than area TE is involved in detecting and processing particular visual shapes.     

The effect of hemidecortication on the inhibitory interactions in the superior colliculus of the cat.

Single neurons were recorded extracellularly from the superficial layers of the superior colliculus (SC) in 21 curarized cats. Four animals were normal unoperated cats, 17 were animals in which all cortical visual areas were ablated on one side from 7 to 69 days before the electrophysiological experiments. After cortical ablation all animals were blind in the visual field contralateral to the ablated side. In both normal and hemianopsic cats the effect of a visual stimulus located very far from the excitatory part of the unit receptive field, on the neuron responses to visual stimuli was studied. The remote stimulus (extra-field stimulus) was a hand moved black spot 10 degrees in diameter. In normal animals the introduction of the extra-field stimulus in the hemifield contralateral or ipsilateral to the recorded SC produced a marked reduction of unit responses to visual stimuli presented in their receptive field. This effect was particularly strong when the extra-field stimuli were introduced in the hemifield contralateral to the recorded side. In the hemianopsic animals the neurons of the SC ipsilateral to the lesion (receptive fields in the behaviorally blind hemifield) responded well to visual stimuli, but were only weakly inhibited by the extra-field stimuli presented in the blind hemifield. The neurons of this colliculus with the exception of those in the upper part of stratum griseum superficiale were normally inhibited by stimuli presented in the normal hemifield. The neurons of the SC contralateral to the lesion responded well to visual stimuli and were normally inhibited by stimuli presented in the normal hemifield; they were virtually not affected by stimuli presented in the blind hemifield. Mechanisms responsible for the abnormal inhibitory interactions between and within colliculi after cortical lesions and the possible behavioral implications of the findings are discussed.     

Characterization of oculomotor and visual activities in the primate pedunculopontine tegmental nucleus during visually guided saccade tasks

The pedunculopontine tegmental nucleus (PPTN) has anatomical connections with numerous visuomotor areas including the basal ganglia, thalamus, superior colliculus and frontal eye field. Although many anatomical and physiological studies suggest a role for the PPTN in the control of conditioned behavior and associative learning, the detailed characteristics of saccade‐ and visual‐related activities of PPTN neurons remain unclear. We recorded the activity of PPTN neurons in monkeys (Macaca fuscata ) during visually guided saccade tasks, and examined the response properties of saccade‐ and visual‐related activities such as time course, direction selectivity and contextual modulation. Saccade‐related activity occurred either during saccade execution or after saccade end. The preferred directions of the neuronal activity were biased toward the contralateral and upward sides. Half of the saccade‐related neurons showed activity modulation only for task saccades and not for spontaneous saccades outside the task. Visually‐responsive neurons responded with short latencies. Some responded to the appearance of the visual stimulus in a directionally selective manner, and others responded to both the appearance and disappearance of the visual stimulus in a directionally non‐selective manner. Many of these neurons exhibited distinct visual responses to the appearance of two different stimuli presented under different stages of the task, whereas a population of the neurons responded equally to the disappearance of the two stimuli. Thus, many PPTN neurons exhibited context‐dependent activity related to the visuomotor events, consistent with a role in controlling conditioned behavior.     

Visual Recognition Is Heralded by Shifts in Local Field Potential Oscillations and Inhibitory Networks in Primary Visual Cortex

Learning to recognize and filter familiar, irrelevant sensory stimuli eases the computational burden on the cerebral cortex. Inhibition is a candidate mechanism in this filtration process, and oscillations in the cortical local field potential (LFP) serve as markers of the engagement of different inhibitory neurons. We show here that LFP oscillatory activity in visual cortex is profoundly altered as male and female mice learn to recognize an oriented grating stimulus—low-frequency (∼15 Hz peak) power sharply increases, whereas high-frequency (∼65 Hz peak) power decreases. These changes report recognition of the familiar pattern as they disappear when the stimulus is rotated to a novel orientation. Two-photon imaging of neuronal activity reveals that parvalbumin-expressing inhibitory neurons disengage with familiar stimuli and reactivate to novelty, whereas somatostatin-expressing inhibitory neurons show opposing activity patterns. We propose a model in which the balance of two interacting interneuron circuits shifts as novel stimuli become familiar.SIGNIFICANCE STATEMENT Habituation, familiarity, and novelty detection are fundamental cognitive processes that enable organisms to adaptively filter meaningless stimuli and focus attention on potentially important elements of their environment. We have shown that this process can be studied fruitfully in the mouse primary visual cortex by using simple grating stimuli for which novelty and familiarity are defined by orientation and by measuring stimulus-evoked and continuous local field potentials. Altered event-related and spontaneous potentials, and deficient habituation, are well-documented features of several neurodevelopmental psychiatric disorders. The paradigm described here will be valuable to interrogate the origins of these signals and the meaning of their disruption more deeply.     

Neural correlates of memory retrieval in the prefrontal cortex

Working memory includes short-term representations of information that were recently experienced or retrieved from long-term representations of sensory stimuli. Evidence is presented here that working memory activates the same dorsolateral prefrontal cortex neurons that: (a) maintained recently perceived visual stimuli; and (b) retrieved visual stimuli from long-term memory (LTM). Single neuron activity was recorded in the dorsolateral prefrontal cortex while trained monkeys discriminated between two orientated lines shown sequentially, separated by a fixed interstimulus interval. This visual task required the monkey to compare the orientation of the second line with the memory trace of the first and to decide the relative orientation of the second. When the behavioural task required the monkey to maintain in working memory a first stimulus that continually changed from trial to trial, the discharge in these cells was related to the parameters--the orientation--of the memorized item. Then, what the monkey had to recall from memory was manipulated by switching to another task in which the first stimulus was not shown, and had to be retrieved from LTM. The discharge rates of the same neurons also varied depending on the parameters of the memorized stimuli, and their response was progressively delayed as the monkey performed the task. These results suggest that working memory activates dorsolateral prefrontal cortex neurons that maintain parametrical visual information in short-term and LTM, and that the contents of working memory cannot be limited to what has recently happened in the sensory environment.     

Impaired habituation in children with attention deficit hyperactivity disorder.

OBJECTIVE: To investigate whether children with attention deficit hyperactivity disorder show impaired habituation to peripheral stimuli. METHOD: We compared the Troxler effect (the ability to habituate to a peripheral visual stimulus when presented with a competing central visual stimulus) in groups of 23 children with attention deficit hyperactivity disorder and 15 controls matched for age, gender, and IQ. RESULTS: Regression analyses revealed a statistically significant effect of diagnosis on fading (P = 0.03), with attention deficit hyperactivity disorder subjects taking longer to fade to a peripheral stimulus than controls. Additional analyses revealed a significant interaction between diagnosis and visual field; control subjects showed similar fading times to stimuli presented in the right and left visual fields (13.25 vs. 12.96 seconds), while the attention deficit hyperactivity disorder group showed much slower fading in the right than in the left visual field (18.64 vs. 15.00 seconds). CONCLUSIONS: Our results suggest that children with attention deficit hyperactivity disorder have impaired visual habituation. The findings provide evidence of frontal dysfunction in attention deficit hyperactivity disorder and suggest that impaired habituation contributes to off-task behavior in children with the disorder.     

Hippocampal neurons in the monkey with activity related to the place in which a stimulus is shown

In order to analyze the functions of the hippocampus in the primate, and to advance the understanding of amnesia, the activity of 994 single hippocampal neurons in the monkey was analyzed during the performance of a task known to be affected by hippocampal damage in which both an object, and its position in space, must be remembered. The serial multiple object-place memory task required a memory for the position on a video monitor in which a given object had appeared previously. It was found that 9.3% of neurons recorded in the hippocampus and hippocampal gyrus had spatial fields in this and related tasks, in that they responded whenever there was a stimulus in some but not in other positions on the screen. We found that 2.4% of the neurons responded to a combination of spatial information and information about the object seen, in that they responded more the first time a particular object was seen in any position. Six of these neurons were found that showed this combination even more clearly, in that, for example, they responded only to some positions and only if it was the first time that a particular stimulus had appeared there. It is concluded that there are neurons in the primate hippocampus which (1) respond to position in space and (2) in some cases combine information about stimuli and their position in space, responding to a stimulus only the first time it is seen in a position in space, for example. Thus, not only is spatial information processed by the primate hippocampus, but it can be combined with information about which stimuli have been seen before. The ability of the hippocampus to form such conjunctions may be an important property for its role in memory.     

Learning and memory is reflected in the responses of reinforcement-related neurons in the primate basal forebrain

Certain basal forebrain neurons encode the learned reinforcement value of objects: they respond differentially to visual stimuli that signal availability of fruit juice (positively reinforcing) or saline (negatively reinforcing) obtained by lick responses in visual discrimination tasks. In this report we describe the rapid, learning-related changes in the responses of these neurons during the acquisition and reversal of the reinforcement contingency of a visual discrimination reversal task. The same neurons also responded differentially to novel and familiar stimuli in 2 recognition memory tasks, in which monkeys applied the learned rule that lick responses to novel stimuli elicited saline and responses to familiar stimuli elicited juice. These differential responses to novel and familiar stimuli thus reflected the reinforcement value of the stimuli. A single presentation of a novel or a familiar stimulus was sufficient to elicit a differential response which was maintained even when the stimulus had not been seen recently. The maintenance of the differential response indicates that these neurons are influenced by a durable memory for the stimuli, estimated to be 30 trials on average. These differential neurons were recorded in the substantia innominata, the diagonal band of Broca, and a periventricular region of the basal forebrain. The responses of the reinforcement-related neurons in these 3 regions were similar in most respects. These results support the conclusion that basal forebrain neurons respond to sensory stimuli that, through learning of different contingencies, signal the availability of reinforcement. We suggest that the properties of learning and memory reflected in these neuronal responses are due to afferent pathways from ventromedial regions of the prefrontal and temporal cortices and the amygdala, and that the responses of these neurons provide an enabling mechanism that facilitates the operation of diverse cortical regions in which specific sensory, motor, or mnemonic functions take place.     

Superior colliculus activity related to attention and to connotative stimulus meaning

Single- and multi-unit activity was recorded from cells in the superior colliculus of two awake monkeys (Macaca fascicularis). 32.5% of 366 investigated units responded while the animals attentively gazed at visual stimuli. 50% of these neurons responded to all stimuli presented, including stationary and moving light bars, whereas the other neurons only responded to specific stimuli like faces or food. The responses of a part of these neurons depended on the connotative stimulus meaning.     

Single unit response types in the pulvinar of the Cebus monkey to multisensory stimulation

Response to sensory stimulation was studied in 162 neurons in the pulvinar of Cebus monkeys in 4 acute and 5 chronic preparations. Two basic response patterns were observed: type I responses, similar to those obtained in primary relay centers, were only observed after visual stimulation. Type II responses were obtained after stimulation of more than one sensory modality. Characteristically these responses presented fatigue and habituation. Temporal relationship between stimulus and response was not as clear as in type I responses, afterdischarge frequently occurred. Taking these response types into consideration two groups of units were identified in the pulvinar. Units of group A (91 neurons) showed type I response to visual stimulation. For these units receptive fields similar to those found in other regions of visual projection could be defined. As a rule units of group A displayed type II responses to other sensory modalities. Units of group B (71) did not display type I responses; they always responded to visual, somatic, auditory and olfactory stimuli with type II responses. They could be activated by a single sensory modality (B, unimodal) or by more than one sensory modality (B, multimodal).     

Imaging population dynamics of surround suppression in the superior colliculus

The superior colliculus (SC) plays a key role in controlling spatial attention. It is hypothesized that some forms of spatial attention, such as the detection of a single salient object arise from lateral competitive interactions between different locations within the spatial map in the SC. This hypothesis is supported by a recent in vitro study showing that a ‘Mexican hat’‐like pattern of synaptic connectivity is implemented in the intrinsic circuit of the superficial layer of the SC (sSC). However, the neuronal population mechanisms responsible for this pattern still remain unclear. Here, we examined how spatial response modulations, for example lateral interactions and surround suppression, are represented at the neuronal population level using in vivo two‐photon calcium imaging in the mouse sSC. Observation of neuronal population responses with single‐cell resolution enabled us to identify a small subset of neurons that were activated by relatively small visual stimuli (< 1° diameter), and thus allowed us to detect the exact location of the ‘response center’ in the sSC to a visual stimulus presented at a given location. We demonstrated that presenting two‐point stimuli or one large stimulus modulated the spatial response pattern of the neuronal population, i.e. centre facilitation and surround suppression. Furthermore, we found that both GABAergic and non‐GABAergic neurons showed a similar population response pattern of surround suppression. The population dynamics suggest the circuit mechanism underlying lateral inhibition and surround suppression may be supported by long‐range inhibitory neurons in the sSC.