Neuronal Sianallina of Information Imoortant to Visual Recognition-Memory in Rat Rhinal aid Neighbouring Cortices

This study was conducted to discover whether the rat cortex contains neurons that signal information concerning the previous occurrence of stimuli, as has been found in the primate. Recordings of the activity of 396 single neurons were made while unanaesthetized rats were shown objects. The effects on neuronal responsiveness of stimulus repetition and of the relative familiarity of the stimuli were sought. The areas sampled were the rhinal (entorhinal and perirhinal) cortex, area TE of the temporal cortex, the lateral occipital cortex and the hippocampal formation. The response to the first presentations of objects was significantly different from that to their second presentations for 63 (34%) of the 185 responsive neurons; for 39 of the neurons the response was smaller when the stimulus was repeated, whereas for 24 it was larger. The incidence of decremental responses was higher in the non-hippocampal cortex than in the hippocampal formation, while the incidence of incremental responses was higher in the hippocampal formation than other cortical areas. The response to unfamiliar objects was significantly different from that to highly familiar objects for 15 (22%) of 67 responsive neurons so tested; for 12 of the neurons the response was smaller when the stimulus was repeated, and for three it was larger; most of these neurons were found in area TE. The responses of ten familiarity neurons varied significantly with the relative familiarity of the stimuli but not with stimulus repetition; the responses of seven recency neurons varied significantly upon stimulus repetition but not with the relative familiarity of the stimuli. Thus information concerning stimulus repetition and familiarity is separably encoded at the single neuron level in the rat cortex. The results demonstrate that in the rat cortex as in the monkey cortex there are neurons that signal information concerning the prior occurrence of stimuli; such information is of importance to recognition memory, working memory and priming memory.     

The effects of visual stimulation and memory on neurons of the hippocampal formation and the neighboring parahippocampal gyrus and inferior temporal cortex of the primate

The activity of 736 single neurons was recorded from the hippocampal formation (HF), the rhinal cortex (RH), the medial and anterior inferior temporal cortex (TE), or areas TF and TH of the parahippocampal gyrus (PHG) of monkeys during the performance of a delayed matching to sample task. The results indicate differences between the areas in their contributions to sensory processing and memory. Of the neurons, 55% responded to either the first (S1) and/or the second (S2) of the two successively presented visual stimuli. The proportion of responsive neurons and the proportion of neurons that responded selectively on the basis of shape or color (but not size) were significantly higher in areas TE + RH than in HF + PHG. The responses to S1 differed from those to S2 for 18% of the total sample: of these differentially responsive neurons, 66% of the TE + RH neurons responded more strongly to S1 (the sample presentation, allowing stimulus acquisition), whereas 71% of the HF + PHG neurons responded more strongly to S2 (the match/nonmatch comparison, when the behavioral decision could be made). Of 239 TE + RH neurons recorded during the delayed matching task or when objects were shown, 12% displayed evidence of memory for the previous occurrence of stimuli by responding strongly to the first, but significantly less strongly to subsequent presentations of visual stimuli that were novel or had not been seen recently. In contrast, none (0%) of 328 neurons so tested in HF and PHG had a response that declined significantly on stimulus repetition. For six (86%) of seven TE + RH neurons tested, the decrement in response persisted even after distraction by intervening presentations of other stimuli. Further evidence of information storage was found for 7 (33%) of 21 neurons for which responses to the first presentations of unfamiliar objects were significantly greater than to the first presentations of very familiar objects, even though the familiar objects had not been seen for greater than 15 min.     

Finding and Not Finding Rat Perirhinal Neuronal Responses to Novelty

There is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in “paired viewing” experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had “object fields”); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition‐related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Perirhinal cortex neuronal activity related to long-term familiarity memory in the macaque

Lesion studies suggest that the perirhinal cortex plays a role in object recognition memory. To analyse its role, the activity of single neurons in the perirhinal cortex was recorded in three rhesus monkeys (Macaca mulatta) performing a delayed matching-to-sample task with up to three intervening stimuli. A set of familiar visual stimuli was used. Some neurons had activity related to working memory, in that they responded more to the sample than to the match image within a trial, as shown previously. However, when a novel set of stimuli was introduced, the neuronal responses were on average only 47% of the magnitude of the responses to the familiar set of stimuli. Moreover, it was shown in eight different replications in three monkeys that the responses of the perirhinal cortex neurons gradually increased over hundreds of presentations of the new set of (initially novel) stimuli to become as large as with the already familiar stimuli. The mean number of 1.3-s presentations to induce this effect was 400 occurring over 7-13 days. These results show that perirhinal cortex neurons represent the very long-term familiarity of visual stimuli. A representation of the long-term familiarity of visual stimuli may be important for many aspects of social behaviour, and part of the impairment in temporal lobe amnesia may be related to the difficulty of building representations of the degree of familiarity of stimuli.     

Cortical representations of personally familiar objects and places: functional organization of the human posterior cingulate cortex

The recognition of both personally familiar objects and places involves nonspatial memory retrieval processes, but only personally familiar places are represented as space. Although the posterior cingulate cortex (PCC) is considered to process both types of such memories, its functional organization is poorly understood. In this event-related fMRI study, normal subjects judged familiar/unfamiliar pictures in four categories: familiar places (FP), familiar objects (FO), unfamiliar places (UP), and unfamiliar objects (UO), thus constituting a two-factorial design. A significant main effect of stimuli with greater activation in the place (FP and UP) than object (FO and UO) trials was observed bilaterally in several medial temporo-occipito-parietal regions, including the caudal PCC (cPCC) and parahippocampal gyrus. The reverse comparison revealed greater activation in the lateral inferior occipito-temporal junctions and intraparietal sulci bilaterally. A significant main effect of familiarity with greater activation in the familiar (FP and FO) than unfamiliar (UP and UO) trials was observed in the mid-dorsal PCC (mPCC), retrosplenial cortex, posterior precuneus, and the left intraparietal sulcus. Activation specific to the FP trials (as assessed by the interaction) was observed in the right posterodorsal PCC (pPCC) only. Together with data from previous functional imaging studies, the results suggest a functional segregation of human PCC with differential involvement of pPCC in spatial representations of personally familiar places and of the mPCC and retrosplenial cortex in episodic retrieval of personally familiar places and objects. Activation of the left intraparietal sulcus may reflect retrieval of memories related to object manipulation.     

Neuronal evidence that inferomedial temporal cortex is more important than hippocampus in certain processes underlying recognition memory

Amnesia has been reported to result from combined damage to the amygdala, hippocampus and inferomedial temporal cortex in man and monkey. Evidence is presented that neuronal activity in the monkey inferomedial temporal cortex reflects memory for the previous occurrence of visual stimuli: 26 (15%) of 173 single units responded more strongly to first than to subsequent presentation of unfamiliar stimuli. No such responses were found for neurones recorded in the hippocampus and subicular cortex. The findings suggest that the inferomedial temporal cortex plays a central role in processes necessary for recognition memory.     

Repetition suppression and effects of familiarity on blood oxygenation level dependent signal and gamma-band activity

We used an identical repetition priming paradigm in functional MRI (fMRI) and magnetoencephalography (MEG) to investigate brain networks modulated by stimulus repetition and familiarity. In particular, pictures of familiar or unfamiliar objects were presented sequentially, with stimulus repetitions occurring within few trials. The results of both studies indicated close agreement between the pattern found in fMRI-BOLD (blood oxygenation level dependent) responses and in source localizations of induced gamma-band activity derived from MEG. In both studies, the brain regions that were significantly associated with repetition suppression in response to familiar visual objects encompassed bilaterally the medial and lateral occipital cortex, inferior occipitotemporal regions including the left fusiform cortex, as well as parietal areas. Modulations by stimulus familiarity occurred mainly within this network. Overall, we found noticeable correspondences between the results of fMRI-BOLD signals and MEG gamma-band activity, suggesting that both methods can be used in analogous ways to study the neural basis of repetition priming and object recognition.     

A study of cortical and brainstem mechanisms of diffuse noxious inhibitory controls in anaesthetised normal and neuropathic rats

Diffuse noxious inhibitory controls (DNIC) are a mechanism of endogenous descending pain modulation and are deficient in a large proportion of chronic pain patients. However, the pathways involved remain only partially determined with several cortical and brainstem structures implicated. This study examined the role of the dorsal reticular nucleus (DRt) and infralimbic (ILC) region of the medial prefrontal cortex in DNIC. In vivo electrophysiology was performed to record from dorsal horn lamina V/VI wide dynamic range neurones with left hind paw receptive fields in anaesthetised sham‐operated and L5/L6 spinal nerve‐ligated (SNL) rats. Evoked neuronal responses were quantified in the presence and absence of a conditioning stimulus (left ear clamp). In sham rats, DNIC were reproducibly recruited by a heterotopically applied conditioning stimulus, an effect that was absent in neuropathic rats. Intra‐DRt naloxone had no effect on spinal neuronal responses to dynamic brush, punctate mechanical, evaporative cooling and heat stimuli in sham and SNL rats. In addition, intra‐DRt naloxone blocked DNIC in sham rats, but had no effect in SNL rats. Intra‐ILC lidocaine had no effect on spinal neuronal responses to dynamic brush, punctate mechanical, evaporative cooling and heat stimuli in sham and SNL rats. However, differential effects were observed in relation to the expression of DNIC; intra‐ILC lidocaine blocked activation of DNIC in sham rats but restored DNIC in SNL rats. These data suggest that the ILC is not directly involved in mediating DNIC but can modulate its activation and that DRt involvement in DNIC requires opioidergic signalling.     

Configural and analytical processing of familiar and unfamiliar objects

Configural processing could develop for non-face visual objects as one becomes familiar with those objects through repeated exposure. To explore the role of familiarity in object recognition, we studied the effect of adaptation to a visual object (adapting stimulus) on the identification performance of other objects (test stimulus) while adapting and test stimuli were exactly the same, shared parts or were completely different. We used a subset of English alphabets (p, q, d and b) as familiar objects and an unfamiliar set of symbols constructed from same parts but with different configurations. Adaptation to a member of each set led to a lower identification performance for that object in a crowding paradigm. Adaptation to each member of the unfamiliar set resulted in decreased identification performance for the same object and those members of the set that shared parts with the adapting stimulus. But no such transfer of adaptation was observed for the familiar set. Our results support the notion that processing of object parts plays an important role in the recognition of unfamiliar objects while recognition of familiar objects is mainly based on configural processing mechanisms.     

The latency of activation of neurones in the lateral hypothalamus and substantia innominata during feeding in the monkey

To investigate whether the responses of neurones in the lateral hypothalamus and substantia innominata associated with the sight of food could control the responses of the hungry monkey to the food, the latency of activation of these neurones by food was measured. It was found that when an electromagnetically operated wide-aperture shutter opened to reveal food or non-food objects, these hypothalamic neurones responded with a latency of 150–200 msec to the food objects, and did not respond to the non-food objects. To measure the latency of the monkey's responses to the food, a visual discrimination task was set in which the monkey could lick a tube to obtain fruit juice if a food-related visual stimulus was shown, but obtained hypertonic saline, which was aversive, if a different visual stimulus was shown. In this situation the typical latencies of the neuronal responses to the food were 150–200 msec, of the lick responses 350–400 msec. and of the EMG activity associated with these lick responses 250–400 msec. Thus the responses of these hypothalamic neurones precede the monkey's responses to the food, and could mediate the feeding and other responses of the animal to the food.It was also shown that a different population of hypothalamic neurones with responses associated with the sight of aversive visual stimuli had response latencies of 150–200 msec.     

Mapping parahippocampal systems for recognition and recency memory in the absence of the rat hippocampus

The present study examined immediate‐early gene expression in the perirhinal cortex of rats with hippocampal lesions. The goal was to test those models of recognition memory which assume that the perirhinal cortex can function independently of the hippocampus. The c‐fos gene was targeted, as its expression in the perirhinal cortex is strongly associated with recognition memory. Four groups of rats were examined. Rats with hippocampal lesions and their surgical controls were given either a recognition memory task (novel vs. familiar objects) or a relative recency task (objects with differing degrees of familiarity). Perirhinal Fos expression in the hippocampal‐lesioned groups correlated with both recognition and recency performance. The hippocampal lesions, however, had no apparent effect on overall levels of perirhinal or entorhinal cortex c‐fos expression in response to novel objects, with only restricted effects being seen in the recency condition. Network analyses showed that whereas the patterns of parahippocampal interactions were differentially affected by novel or familiar objects, these correlated networks were not altered by hippocampal lesions. Additional analyses in control rats revealed two modes of correlated medial temporal activation. Novel stimuli recruited the pathway from the lateral entorhinal cortex (cortical layer II or III) to hippocampal field CA3, and thence to CA1. Familiar stimuli recruited the direct pathway from the lateral entorhinal cortex (principally layer III) to CA1. The present findings not only reveal the independence from the hippocampus of some perirhinal systems associated with recognition memory, but also show how novel stimuli engage hippocampal subfields in qualitatively different ways from familiar stimuli.     

Neuronal activity in the cerebellar interpositus and lateral pontine nuclei during inhibitory classical conditioning of the eyeblink response

Single-unit neuronal activity was recorded from the cerebellar interpositus nucleus and lateral pontine nuclei during conditioned inhibition of the eyeblink response in rats. Conditioned inhibition training sessions included 100 trials/day for 12 days. During each training session, the rats were given 50 presentations of a tone conditioned stimulus (CS) that was paired with a brief periocular shock unconditioned stimulus (US). They were also given 50 presentations of a compound stimulus that included the tone-CS and a light-CS. The compound-CS was not paired with the US. The two types of trials were mixed throughout the session and presented in an irregular sequence. This training procedure resulted in significant inhibition of the eyeblink response during the compound-CS. Neurons in the interpositus and lateral pontine nuclei exhibited significantly less activity during the compound-CS relative to the tone-CS. The suppression of cerebellar and pontine learning-related neuronal activity during the inhibitory CS may be critical for inhibiting the conditioned eyeblink response.     

Perirhinal cortex lesions uncover subsidiary systems in the rat for the detection of novel and familiar objects

The present study compared the impact of perirhinal cortex lesions on tests of object recognition. Object recognition was tested directly by looking at the preferential exploration of novel objects over simultaneously presented familiar objects. Object recognition was also tested indirectly by presenting just novel objects or just familiar objects, and recording exploration levels. Rats with perirhinal cortex lesions were severely impaired at discriminating a novel object from a simultaneously presented familiar object (direct test), yet displayed normal levels of exploration to novel objects presented on their own and showed normal declines in exploration times for familiar objects that were repeatedly presented (indirect tests). This effective reduction in the exploration of familiar objects after perirhinal cortex lesions points to the sparing of some recognition mechanisms. This possibility led us to determine whether rats with perirhinal cortex lesions can overcome their preferential exploration deficits when given multiple object familiarisation trials prior to that same (familiar) object being paired with a novel object. It was found that after multiple familiarisation trials, objects could now successfully be recognised as familiar by rats with perirhinal cortex lesions, both following a 90-min delay (the longest delay tested) and when object recognition was tested in the dark after familiarisation trials in the light. These latter findings reveal: (i) the presumed recruitment of other regions to solve recognition memory problems in the absence of perirhinal cortex tissue; and (ii) that these additional recognition mechanisms require more familiarisation trials than perirhinal-based recognition mechanisms.     

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.     

Medullospinal vasomotor neurones mediate hypotension from stimulation of prefrontal cortex.

Electrical stimulation of the prefrontal cortex in anaesthetised, paralysed rats evokes transient hypotension. In this study we have endeavoured to determine whether this evoked response is mediated by the spinal cord-projecting vasomotor neurones of the rostroventrolateral medulla (RVL). The responses of RVL-spinal vasomotor neurones to electrical stimulation of the prefrontal cortex caused a period of inhibition of the neuronal activity in the majority of cases (11 out of 13 neurones tested, 85%) and a short period of excitation in the remaining 2 neurones (15%). The prefrontal cortex-evoked inhibition of RVL-spinal vasomotor neurones was eliminated by iontophoretic application of bicuculline, a GABAa receptor antagonist, to the RVL-spinal vasomotor neurones. Microinjection of 50 nl of bicuculline methiodide into the same area of the RVL where the neurones have been identified converted the prefrontal-evoked hypotension into a vasopressor response. These findings indicate that the hypotension evoked by stimulating the prefrontal cortex is mediated by GABAergic inhibition of the RVL-spinal vasomotor neurones.     

Activity of neurones in the inferotemporal cortex of the alert monkey.

The activity of neurones in the inferotemporal cortex of the alert rhesus monkey was recorded while the monkey was shown visual stimuli, which included both food and non-food objects for comparison with the activity of neurones in the lateral hypothalamus and substantia innominata. In the anteroventral part of the inferotemporal cortex, neurones were found with visual responses which were sustained while the animal looked at the appropriate visual stimuli. The latency of the responses was 100 msec or more. The majority (96/142 or 68%) of these neurones responded more strongly to some stimuli than to others. These units usually had different responses when objects were shown from different views, and physical factors such as shape, size, orientation, colour and texture appeared to account for the responses of some of these units. Association of visual stimuli with a food reward (glucose solution) or an aversive taste (5% saline solution) did not affect the magnitude of the responses of the neurones to the stimuli either during the learning or after the period of learning. Nor did feeding the monkey to satiety affect the responses of the neurones to their effective stimuli.     

Classical conditioning modifies cytochrome oxidase activity in the auditory system

The effects of excitatory classical conditioning on cytochrome oxidase activity in the central auditory system were investigated using quantitative histochemistry. Rats in the conditioned group were trained with consistent pairings of a compound conditional stimulus (a tone and a light) with a mild footshock, to elicit conditioned suppression of drinking. Rats in the pseudorandom group were exposed to pseudorandom presentations of the same tone, light and shock stimuli without consistent pairings. Untrained rats in a naive group did not receive presentations of the experimental stimuli.
 The findings demonstrated that auditory fear conditioning modifies the metabolic neuronal responses of the auditory system, supporting the hypothesis that sensory neurons are responsive to behavioural stimulus properties acquired by learning. There was a clear distinction between thalamocortical and lower divisions of the auditory system based on the differences in metabolic activity evoked by classical conditioning, which lead to an overt learned behavioural response versus pseudorandom stimulus presentations, which lead to behavioural habituation. Increases in cytochrome oxidase activity indicated that tone processing is enhanced during associative conditioning at upper auditory structures (medial geniculate nucleus and secondary auditory cortices). In contrast, metabolic activation of lower auditory structures (cochlear nuclei and inferior colliculus) in response to the pseudorandom presentation of the experimental stimuli suggest that these areas may be activated during habituation to tone stimuli. Together these findings show that mapping the metabolic activity of cytochrome oxidase with quantitative histochemistry can be successfully used to map regional long‐lasting effects of learning on brain systems.     

Simultanagnosia: effects of semantic category and repetition blindness

When confronted with two identical stimuli in a very brief period of time subjects often fail to report the second stimulus, a phenomenon termed "repetition blindness". The "type-token" account attributes the phenomenon to a failure to individuate the exemplars. We report a subject, KE, who developed simultanagnosia (the inability to see more than one item in an array) as a consequence of bilateral parietal lobe infarctions. With presentation of two words, pictures or letters for an unlimited time, KE typically reported both stimuli on less than half of trials. Performance was significantly influenced by the semantic relationship between items in the array. He reported both items significantly more frequently if they were semantically related; in contrast, when presented either identical or visually different depictions of the same item, he reported both items on only 2-4% of trials. Performance was not influenced by the visual similarity between the stimuli; he reported visually dissimilar objects less frequently than visually similar but different objects. We suggest that KE's bilateral parietal lesions prevent the binding of preserved object representations to a representation computed by the dorsal visual system. More generally, these data are consistent with the claim that the posterior parietal cortex is crucial for individuating a stimulus by computing its unique spatio-temporal characteristics.     

Diminution of evoked neuronal activity in the visual cortex of pattern deprived rats

The “deprived” cortex of monocularly deprived rats showed a considerable diminution in response to specific visual stimuli. Many neurons (57.7%) in the “deprived” cortex did not respond to any visual stimuli, and 29% reacted nonspecifically to any stimulus anywhere in the visual field (indefinite cells). In comparison, 7.4% neurons in the “nondeprived” cortex were not responsive to visual stimuli and 41.3% gave indefinite response. In the “normal” cortex 51.1% of the cells were motion, orientation, or direction selective while the number for the “deprived” cortex was 13.3%. Spontaneous activity of the “deprived” cells was of the same rate and pattern as was that of the “normal” cells. Receptive field properties of cells from the “deprived” cortex that were responsive, were similar to those of cells from the “normal” cortex. They were large and showed pure “on” “off” or “on-off” regions; others were of the complex type with mixed response regions. All responded optimally to moving stimuli.     

Heterogeneity in the coding in rat barrel cortex of the velocity of protraction of the macrovibrissae

Rats whisk to explore their environment and obtain information on object features, and the responses of somatosensory cortical neurones must precisely encode aspects of whisker movements. Using trapezoidal stimuli to deflect whiskers, with a wide range of velocities and amplitudes of whisker protraction, we recorded responses from a relatively homogeneous population of isolated cells and neuronal multiunits within the postero-medial barrel sub-field of somatosensory cortex, and analysed responses in an early post-stimulus-onset window. For 92% of neurones the function relating response strength to velocity was a saturating sigmoid but there were differences between neurones in the slopes and ranges over which responses changed. Responses of other neurones were non-monotonic, with response strength decaying at very high whisker deflection velocities. Generally, barrel cortex neurones were responsive to a much wider range of whisker protraction velocities than hitherto reported, especially to much slower velocities than generally assumed to be the main range of sensitivity. This carries implications for coding of whisker deflection velocity, a parameter that appears to be a significant information-bearing element of natural whisking. The effect of amplitude of deflection upon neural responses was evident in only approximately 24% of units and only when the dominant velocity effect had saturated.