Impairments in visual discrimination after perirhinal cortex lesions: testing 'declarative' vs. 'perceptual-mnemonic' views of perirhinal cortex function

Two experiments tested the predictions of 'declarative' vs. 'perceptual-mnemonic' views of perirhinal cortex function. The former view predicts that perirhinal cortex lesions should impair rapidly learned, but not more slowly learned, visual discriminations, whereas the latter view predicts that impairments should be related not to speed of learning but to perceptual factors. It was found that monkeys with perirhinal cortex lesions were impaired in the acquisition and performance of slowly learned, perceptually difficult greyscale picture discriminations, but were not impaired in the acquisition of rapidly learned, perceptually easier discriminations. In addition, these same monkeys were not impaired in the acquisition or performance of difficult colour or size discriminations, indicating that the observed pattern of impairments was not due to ceiling effects or difficulty per se. These findings, taken together, are consistent with the 'perceptual-mnemonic' view that the perirhinal cortex is involved in both perception and memory, but are not consistent with the 'declarative' view that the perirhinal cortex is important exclusively for declarative memory, having little or no role in perception. Moreover, the results are consistent with the more specific proposal that the perirhinal cortex contributes to the solution of complex visual discriminations with a high degree of 'feature ambiguity', a property of visual discrimination problems that can emerge when features of an object are rewarded when part of one object, but not when part of another. These and other recent findings suggest the need for a revision of prevailing views regarding the neural organization of perception and memory.     

The organization of visual object representations: a connectionist model of effects of lesions in perirhinal cortex

We have developed a simple connectionist model based on the idea that perirhinal cortex has properties similar to other regions in the ventral visual stream, or 'what' pathway. The model is based on the assumption that representations in the ventral visual stream are organized hierarchically, such that representations of simple features of objects are stored in caudal regions of the ventral visual stream, and representations of the conjunctions of these features are stored in more rostral regions. We propose that a function of these feature conjunction representations is to help to resolve 'feature ambiguity', a property of visual discrimination problems that can emerge when features of an object predict a given outcome (e.g. reward) when part of one object, but predict a different outcome when part of another object. Several recently reported effects of lesions of perirhinal cortex in monkeys have provided key insights into the functions of this region. In the present study these effects were simulated by comparing the performance of connectionist networks before and after removal of a layer of units corresponding to perirhinal cortex. The results of these simulations suggest that effects of lesions in perirhinal cortex on visual discrimination may be due not to the impairment of a specific type of learning or memory, such as declarative or procedural, but to compromising the representations of visual stimuli. Furthermore, we propose that attempting to classify perirhinal cortex function as either 'perceptual' or 'mnemonic' may be misguided, as it seems unlikely that these broad constructs will map neatly onto anatomically defined regions of the brain.     

Perirhinal cortex resolves feature ambiguity in complex visual discriminations

The present experiment tested predictions of a 'perceptual-mnemonic/feature conjunction' (PMFC) model of perirhinal cortex function. The model predicts that lesions of perirhinal cortex should disrupt complex visual discriminations with a high degree of 'feature ambiguity', a property of visual discrimination problems that can emerge when features of an object are rewarded when they are part of one object, but not when part of another. As feature ambiguity is thought to be the critical factor, such effects should be independent of the number of objects to be discriminated. This was tested directly, by assessing performance of control monkeys and monkeys with aspiration lesions of perirhinal cortex on a series of concurrent discriminations in which the number of object pairs was held constant, but the degree of feature ambiguity was varied systematically. Monkeys were tested in three conditions: Maximum Feature Ambiguity, in which all features were explicitly ambiguous (AB+, CD+, BC-, AD-; the biconditional problem); Minimum Feature Ambiguity, in which no features were explicitly ambiguous (AB+, CD+, EF-, GH-); and Intermediate Feature Ambiguity, in which half the features were explicitly ambiguous (AB+, CD+, CE-, AF-). The pattern of results closely matched that predicted by simulations using a connectionist network: monkeys with perirhinal cortex lesions were unimpaired in the Minimum Feature Ambiguity condition, mildly impaired in the Intermediate Feature Ambiguity condition and severely impaired in the Maximum Feature Ambiguity condition. These results confirm the predictions of the PMFC model, and force a reconsideration of prevailing views regarding perirhinal cortex function.     

No effect of hippocampal lesions on perirhinal cortex-dependent feature-ambiguous visual discriminations

Previous studies have shown that perirhinal cortex lesions in monkeys impair visual discriminations with a high degree of "feature ambiguity," a property of visual discriminations that can emerge when features are a part of both rewarded and unrewarded stimuli. The effects of damage to the hippocampus on these perirhinal-dependent feature-ambiguous tasks are, however, unknown. Prominent theories of medial temporal lobe function predict similar effects of perirhinal cortex and hippocampal lesions on cognitive tasks. In contrast, our hypothesis is that perirhinal cortex, and not the hippocampus, is important for nonspatial complex feature-ambiguous discriminations. We sought to distinguish between these competing theories in a straightforward way, by testing rhesus monkeys with hippocampal lesions on the same feature-ambiguous tasks shown previously to depend on perirhinal cortex. It was found that hippocampal lesions had no effects on any of these tasks. The findings support the perceptual-mnemonic/feature conjunction model of perirhinal cortex function, and provide further evidence for heterogeneity of function within the putative medial temporal lobe memory system.     

PKMζ maintains 1‐day‐ and 6‐day‐old long‐term object location but not object identity memory in dorsal hippocampus

Continuous activity of the atypical protein kinase C isoform M zeta (PKMζ) is necessary for maintaining long‐term memory acquired in aversively or appetitively motivated associative learning tasks, such as active avoidance, aversive taste conditioning, auditory and contextual fear conditioning, radial arm maze, and watermaze. Whether unreinforced, nonassociative memory will also require PKMζ for long‐term maintenance is not known. Using recognition memory for object location and object identity, we found that inactivating PKMζ in dorsal hippocampus abolishes 1‐day and 6‐day‐old long‐term recognition memory for object location, while recognition memory for object identity was not affected by this treatment. Memory for object location persisted for no more than 35 days after training. These results suggest that the dorsal hippocampus mediates long‐term memory for where, but not what things have been encountered, and that PKMζ maintains this type of spatial knowledge as long as the memory exists. © 2009 Wiley‐Liss, Inc.     

Conditional self‐discrimination enhances dendritic spine number and dendritic length at prefrontal cortex and hippocampal neurons of rats

We studied conditional self‐discrimination (CSD) in rats and compared the neuronal cytoarchitecture of untrained animals and rats that were trained in self‐discrimination. For this purpose, we used thirty 10‐week‐old male rats were randomized into three groups: one control group and two conditioning groups: a comparison group (associative learning) and an experimental group (self‐discrimination). At the end of the conditioning process, the experimental group managed to discriminate their own state of thirst. After the conditioning process, dendritic morphological changes in the pyramidal neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus were evaluated using Golgi‐Cox stain method and then analyzed by the Sholl method. Differences were found in total dendritic length and spine density. Animals trained in self‐discrimination showed an increase in the dendritic length and the number of dendritic spines of neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus. Our data suggest that conditional self‐discrimination improves the connectivity of the prefrontal cortex and dorsal CA1, which has implications for memory and learning processes. Synapse 69:543–552, 2015 . © 2015 Wiley Periodicals, Inc.     

The neuropeptide‐12 improves recognition memory and neuronal plasticity of the limbic system in old rats

Aging is a stage of life where cognitive and motor functions are impaired. This is because oxidative and inflammatory processes exacerbate neurodegeneration, which affects dendritic morphology and neuronal communication of limbic regions with memory loss. Recently, the use of trophic substances has been proposed to prevent neuronal deterioration. The neuropeptide‐12 (N‐PEP‐12) has been evaluated in elderly patients with dementia, showing improvements in cognitive tasks due to acts as a neurotrophic factor. In the present work, we evaluated the effect of N‐PEP‐12 on motor activity and recognition memory, as well as its effects on dendritic morphology and the immunoreactivity of GFAP, Synaptophysin (SYP), and BDNF in neurons of the prefrontal cortex (PFC), dorsal hippocampus (DH) and nucleus accumbens (NAcc) of aged rats. The results show that N‐PEP‐12 improved the recognition memory, but the motor activity was not modified compared to the control animals. N‐PEP‐12 increases the density of dendritic spines and the total dendritic length in neurons of the PFC (layers 3 and 5) and in DH (CA1 and CA3). Interestingly NAcc neurons showed a reduction in the number of dendritic spines. In the N‐PEP‐12 animals, when evaluating the immunoreactivity for SYP and BDNF, there was an increase in the three brain regions, while the mark for GFAP decreased significantly. Our results suggest that N‐PEP‐12 promotes neuronal plasticity in the limbic system of aged animals, which contributes to improving recognition memory. In this sense, N‐PEP‐12 can be considered as a pharmacological alternative to prevent or delay brain aging and control senile dementias.     

Acyl ghrelin improves cognition,synaptic plasticity deficits and neuroinflammation following amyloid β (Aβ1‐40) administration in mice

Ghrelin is a metabolic hormone that has neuroprotective actions in a number of neurological conditions, including Parkinson's disease (PD), stroke and traumatic brain injury. Acyl ghrelin treatment in vivo and in vitro also shows protective capacity in Alzheimer's disease (AD). In the present study, we used ghrelin knockout (KO) and their wild‐type littermates to test whether or not endogenous ghrelin is protective in a mouse model of AD, in which human amyloid β peptide 1‐40 (Aβ_1‐40) was injected into the lateral ventricles i.c.v. Recognition memory, using the novel object recognition task, was significantly impaired in ghrelin KO mice and after i.c.v. Aβ_1‐40 treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Spatial orientation, as assessed by the Y‐maze task, was also significantly impaired in ghrelin KO mice and after i.c.v. Aβ_1‐40 treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Ghrelin KO mice had deficits in olfactory discrimination; however, neither i.c.v. Aβ_1‐40 treatment, nor acyl ghrelin injections affected olfactory discrimination. We used stereology to show that ghrelin KO and Aβ_1‐40 increased the total number of glial fibrillary acidic protein expressing astrocytes and ionised calcium‐binding adapter expressing microglial in the rostral hippocampus. Finally, Aβ_1‐40 blocked long‐term potentiation induced by high‐frequency stimulation and this effect could be acutely blocked with co‐administration of acyl ghrelin. Collectively, our studies demonstrate that ghrelin deletion affects memory performance and also that acyl ghrelin treatment may delay the onset of early events of AD. This supports the idea that acyl ghrelin treatment may be therapeutically beneficial with respect to restricting disease progression in AD.