Alexander Easton - Academia.edu (original) (raw)

Papers by Alexander Easton

Neurobiology of Learning and Memory

Brain and Neuroscience Advances

For the first time, we assess episodic simulation in a patient with visual memory deficit amnesia... more For the first time, we assess episodic simulation in a patient with visual memory deficit amnesia, following damage to visual association cortices. Compared to control participants, the patient with visual memory deficit amnesia shows severely restricted responses when asked to simulate different types of future episodic scenarios. Surprisingly, the patient’s responses are more limited in cases where the scenarios require less reliance on visual information. We explain this counterintuitive finding through discussing how the severe retrograde amnesia in visual memory deficit amnesia limits the patient’s access to episodic memories in which vision has not been a focus of their life. As a result, we argue that the deficits in visual memory deficit amnesia continue to distinguish it from amnesia after direct damage to the hippocampus.

Frontiers in behavioral neuroscience, 2018

Spontaneous recognition tasks are widely used as a laboratory measure of memory in animals but gi... more Spontaneous recognition tasks are widely used as a laboratory measure of memory in animals but give rise to high levels of behavioral noise leading to a lack of reliability. Previous work has shown that a modification of the procedure to allow continual trials testing (in which many trials are run concurrently in a single session) decreases behavioral noise and thus significantly reduces the numbers of rats required to retain statistical power. Here, we demonstrate for the first time that this improved method of testing extends to mice, increasing the overall power of the approach. Moreover, our results show that the new continual trials approach provides the additional benefits of heightened sensitivity and thus provides greater insight into the mechanisms at play. Standard (c57) and transgenic Alzheimer model (TASTPM) mice were tested both at 7 and 10 months of age in both object recognition (OR) and object-location (OL) spontaneous recognition tasks using the continual trials met...

The Cognitive Neuroscience of Social Behaviour, 2005

Frontiers in Behavioral Neuroscience, 1970

The European Journal of Neuroscience, Apr 1, 2008

Both frontal-inferotemporal disconnection and fornix transection (Fx) in the monkey impair object... more Both frontal-inferotemporal disconnection and fornix transection (Fx) in the monkey impair object-in-place scene learning, a model of human episodic memory. If the contribution of the fornix to scene learning is via interaction with or modulation of frontal-temporal interaction ) that is, if they form a unitary system ) then Fx should have no further effect when added to frontal-temporal disconnection. However, if the contribution of the fornix is to some extent distinct, then fornix lesions may produce an additional deficit in scene learning beyond that caused by frontal-temporal disconnection. To distinguish between these possibilities, we trained three male rhesus monkeys on the object-in-place scene-learning task. We tested their learning on the task following frontal-temporal disconnection, achieved by crossed unilateral aspiration of the frontal cortex in one hemisphere and the inferotemporal cortex in the other, and again following the addition of Fx. The monkeys were significantly impaired in scene learning following frontal-temporal disconnection, and furthermore showed a significant increase in this impairment following the addition of Fx, from 32.8% error to 40.5% error (chance ¼ 50%). The increased impairment following the addition of Fx provides evidence that the fornix and frontalinferotemporal interaction make distinct contributions to episodic memory.

Behav Neurosci, 2000

Seven monkeys learned new object-reward associations and scene problems and were overtrained on 1... more Seven monkeys learned new object-reward associations and scene problems and were overtrained on 100 problems of each type. Four monkeys received crossed lesions of the medial forebrain bundle (MFB) and inferior temporal cortex, with the later addition of a fornix section ipsilateral to the MFB lesion. The remaining 3 monkeys received bilateral perirhinal cortex ablation. Disconnection of the MFB from the inferior temporal cortex impaired postoperative new learning, but the retrieval of problems overtrained preoperatively was relatively preserved. Subjects with perirhinal cortex ablation were severely impaired in new learning and at the retrieval of scene problems, but retention of object-reward associations was relatively well preserved. The results support the hypothesis that isolation of the inferior temporal cortex from basal forebrain and midbrain afferents results in dense anterograde amnesia, whereas the role of the perirhinal cortex in learning is dependent on the perceptual difficulty of the task.

Handbook of Behavioral Neuroscience, 2008

ABSTRACT We often consider episodic memory in operational terms as what happened, where, and when... more ABSTRACT We often consider episodic memory in operational terms as what happened, where, and when. Here we consider that the memory of when an event occurred might not be especially important in defining a memory, or even be effectively processed within the episodic memory system. Therefore, we reconsider the relevance of a memory for time to episodic memory and consider an alternative that of “which occasion.” This alternative can encompass elements of temporal coding when necessary or important, but does not restrict the memory to having a temporal element. Redefining episodic memory in this way allows us to develop alternative tests of episodic memory in animals, which provide an opportunity to explore the neural basis of episodic memory.

Frontiers in Behavioral Neuroscience, 2009

Neuroscience and biobehavioral reviews, 2015

This review will consider how spontaneous tasks have been applied alongside neuroscientific techn... more This review will consider how spontaneous tasks have been applied alongside neuroscientific techniques to test complex forms of recognition memory for objects and their environmental features, e.g. the spatial location of an object or the context in which it is presented. We discuss studies that investigate the roles of the perirhinal cortex and the hippocampus in recognition memory using standard testing paradigms, and consider how these findings contribute to the ongoing debate about whether recognition memory is a single unitary process or multiple processes that can be dissociated anatomically and functionally. Due to the wide use of spontaneous tasks, the need for improved procedures that reduce animal use is acknowledged, with multiple trial paradigms discussed as a novel way of reducing variability and animal numbers in these tasks. The importance of improving translation of animal models to humans is highlighted, with emphasis on a shift away from relying on the phenomenolog...

Behavioural brain research, Jan 15, 2015

In recent years, spontaneous recognition tasks have become commonplace methods of assessing memor... more In recent years, spontaneous recognition tasks have become commonplace methods of assessing memory in animals. Adaptations of these tasks allow us to look at the role of objects, contexts and spatial locations in memory. Recent findings have highlighted that not all types of contexts in these tasks rely on the same neural systems. Similarly, asking different questions about the same types of context can allow the dissociation of neural systems underlying these memories. Here we review the current position in how context is used in such tasks, and we consider the fundamental importance of clearly defining both the nature of the context being used, and the questions asked of it in order to fully appreciate the neural and cognitive mechanisms being studied in such tasks.

Experimental brain research, 2003

The marmoset ( Callithrix jacchus) is a small New World monkey that is increasingly being used in... more The marmoset ( Callithrix jacchus) is a small New World monkey that is increasingly being used in a laboratory setting. A previous set of studies has provided a direct comparison between the performance of rats and macaque monkeys on a spatial delayed non-match to sample task in a T-maze (Murray et al. 1989, Experimental Brain Research 74:173-186; Markowska et al. 1989, Experimental Brain Research 74:187-201). In the current experiment we replicated these studies using the marmoset. This allowed for a comparison of the behavioural performance of the marmoset with both rats and macaque monkeys. Marmosets performed well at the task, performing better than macaques, and at a similar level to rats. A closer analysis of the data from the present experiment suggests that marmosets spontaneously alternated in the T-maze, a strategy often adopted by rats, but not by macaques in the T-maze.

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2002

Macaque monkeys learned a strategy task in which two groups of visual objects needed to be treate... more Macaque monkeys learned a strategy task in which two groups of visual objects needed to be treated differently, one with persistent and one with sporadic object choices, to obtain food rewards. After preoperative training, they were divided into two surgical groups of three monkeys each. One group received crossed unilateral removals of frontal cortex and inferior temporal cortex (IT x FC) and were severely impaired in performing the strategy task. The other group received bilateral transection of anterior temporal stem, amygdala, and fornix (TS+AM+FX) and were unimpaired in performing the strategy task. Subsequently the same animals were tested in visual object-reward association learning. Here, confirming previous results, group IT x FC was unimpaired, whereas group TS+AM+FX was severely impaired. The results show that the amnesic effects of TS+AM+FX cannot be generally attributed to the partial temporal-frontal disconnection that this lesion creates, and therefore support the hyp...

Visual Neuroscience, 2002

It is well established that the responses of neurons in the lateral geniculate nucleus (LGN) can ... more It is well established that the responses of neurons in the lateral geniculate nucleus (LGN) can be modulated by feedback from visual cortex, but it is still unclear how cortico-geniculate afferents regulate the flow of visual information to the cortex in the primate. Here we report the effects, on the gain of LGN neurons, of differentially stimulating the extraclassical receptive field, with feedback from the striate cortex intact or inactivated in the marmoset monkey, Callithrix jacchus. A horizontally oriented grating of optimal size, spatial frequency, and temporal frequency was presented to the classical receptive field. The grating varied in contrast (range: 0-1) from trial to trial, and was presented alone, or surrounded by a grating of the same or orthogonal orientation, contained within either a larger annular field, or flanks oriented either horizontally or vertically. V1 was ablated to inactivate cortico-geniculate feedback. The maximum firing rate of LGN neurons was greater with V1 intact, but was reduced by visually stimulating beyond the classical receptive field. Large horizontal or vertical annular gratings were most effective in reducing the maximum firing rate of LGN neurons. Magnocellular neurons were most susceptible to this inhibition from beyond the classical receptive field. Extraclassical inhibition was less effective with V1 ablated. We conclude that inhibition from beyond the classical receptive field reduces the excitatory influence of V1 in the LGN. The net balance between cortico-geniculate excitation and inhibition from beyond the classical receptive field is one mechanism by which signals relayed from the retina to V1 are controlled.

Hippocampus, 2007

Memory for a previously experienced event such as seeing a particular object can involve either a... more Memory for a previously experienced event such as seeing a particular object can involve either a sense of familiarity for the object or of recall for seeing the object on a particular occasion. In humans, it has been claimed that recall and familiarity can be selectively impaired as they are based on dissociable neural systems. However, most tasks used to test memory in nonhuman animals use recognition memory tasks, in which successful performance can be based entirely on familiarity cues. Without the means to selectively investigate recall and familiarity in nonhuman animals, it has until recently proved difficult to dissociate the neural basis of these processes, and their very existence as separable entities has been questioned. Here we discuss a number of studies from our laboratory in which we have developed tasks that require recall and contrast these with recognition memory tasks that can be performed using familiarity alone. We use these tasks to begin to unravel familiarity and recall in the rat and the underlying neural bases of these processes. V V C 2007 Wiley-Liss, Inc.

Hippocampus, 2009

It has been argued that a neural system including the hippocampus, fornix, mamillary bodies, and ... more It has been argued that a neural system including the hippocampus, fornix, mamillary bodies, and anterior thalamus is specifically involved in recollection, but not in familiarity based memory processes. Here we test this hypothesis using a task of episodic-like memory within an E-shaped maze. Animals seek out a preferred object (what) in a particular location (where) that is unique to a particular context (which occasion). As objects are hidden from view at the point of decision making, the animals can only base their decision on recall of their previous episode in the E-shaped maze. In contrast, once a decision has been made animals are free to explore both objects and display an object preference when objects are visible to the animal and decisions can be made on the basis of familiarity. Animals with fornix lesions are impaired at recalling a past event. However, the same animals on the same trials show no such impairment in a judgement of familiarity. We therefore demonstrate that recall is dependent upon the fornix, while familiarity based memory is not. V V C 2009 Wiley-Liss, Inc.

Hippocampus, 2010

Loss of cholinergic cortical input is associated with diseases in which episodic memory impairmen... more Loss of cholinergic cortical input is associated with diseases in which episodic memory impairment is a prominent feature, but the degree to which this neurochemical lesion can account for memory impairment in humans with neurodegenerative diseases remains unclear. Removal of cholinergic input to hippocampus impairs some of its functions in memory, perhaps by reducing the plasticity of information representation within the hippocampus, but the role of cholinergic hippocampal input in episodic-like memories has not been investigated. To address this question, we tested rats with selective lesions of basal forebrain neurons in the medial septum and vertical limb of the diagonal band (MS/VDB), which contains hippocampal-projecting cholinergic neurons, on a task of integrated memory for objects, places, and contexts (''what-where-which'' memory). This task serves as a rodent model of human episodic memory (episodic-like memory) and is sensitive to damage to the hippocampal system. Rats with lesions of cholinergic MS/VDB neurons performed as well on the what-where-which task as controls, but were impaired in a task that simply required them to associate places with contexts (''where-which'' memory). Thus, episodiclike memories that rely on the hippocampus do not require cholinergic neuromodulation to be formed. Nevertheless, some more specific aspects of where-which memory, which may be more dependent on the plasticity of hippocampal spatial representations, require acetylcholine. These results suggest that cholinergic projections to hippocampus are not necessary for episodic memory and, furthermore, that hippocampal spatial representations may be to some extent dissociable from episodic memory function. V V C 2010 Wiley-Liss, Inc.

Philosophical Transactions of The Royal Society B: Biological Sciences, 2002

Colour and greyscale (black and white) pictures look different to us, but it is not clear whether... more Colour and greyscale (black and white) pictures look different to us, but it is not clear whether the difference in appearance is a consequence of the way our visual system uses colour signals or a by-product of our experience. In principle, colour images are qualitatively different from greyscale images because they make it possible to use different processing strategies. Colour signals provide important cues for segmenting the image into areas that represent different objects and for linking together areas that represent the same object. If this property of colour signals is exploited in visual processing we would expect colour stimuli to look different, as a class, from greyscale stimuli. We would also expect that adding colour signals to greyscale signals should change the way that those signals are processed. We have investigated these questions in behavioural and in physiological experiments.

Neuropsychologia, 2012

Acetylcholine has long been implicated in memory, including hippocampal-dependent memory, but the... more Acetylcholine has long been implicated in memory, including hippocampal-dependent memory, but the specific role for this neurotransmitter is difficult to identify in human neuropsychology. Here, we review the evidence for a mechanistic model of acetylcholine function within the hippocampus and consider its explanatory power for interpreting effects resulting from both pharmacological anticholinergic manipulations and lesions of the cholinergic input to the hippocampus in animals. We argue that these effects indicate that acetylcholine is necessary for some, but not all, hippocampal-dependent processes. We review recent evidence from lesion, pharmacological and electrophysiological studies to support the view that a primary function of septohippocampal acetylcholine is to reduce interference in the learning process by adaptively timing and separating encoding and retrieval processes. We reinterpret cholinergic-lesion based deficits according to this view and propose that acetylcholine reduces the interference elicited by the movement of salient locations between events.