Cannabis has been used medicinally for millennia, but the cannabinoid (CB) field exploded with the identification of its endogenous receptors and endocannabinoids (eCBs). In vitro experimentation established that eCBs alter synaptic plasticity at presynaptic nerve terminals; however, the characterization of the eCB system (ECS) in vivo remains incomplete. This study aimed to determine the mechanism of in vivo eCB-mediated hippocampal synaptic plasticity and to analyze the effects this plasticity had on spatial working memory (SWM). With in vivo recordings of field excitatory postsynaptic potentials (fEPSPs) in anesthetized mice and rats as well as pharmacological manipulation of the ECS and glutamate receptor antagonism, it was found that eCBs, both anandamide (AEA) and 2-arachnidonyl glycerol (2-AG), caused LTD at hippocampal CA3-CA1 synapses. Induction of eCB-LTD occurs via a sequential activation of cannabinoid type-1 receptor (CB1R) and NR2B-containing NMDA receptor (NR2BR) and is expressed through the endocytosis of AMPA receptors (AMPARs). Increased eCB tone also caused an impairment of SWM for over 24 hours in the Delayed Non-Match-To-Sample (DNMTS) T-maze. This study provides the first evidence that an acute administration of eCB degradative enzyme inhibitors not only produces an in vivo LTD at hippocampal CA3-CA1 synapses that requires CB1R, NR2BR, and AMPAR, but also impairs SWM, a phenomenon also caused by an acute injection of exogenous CBs.

Cannabis has been used medicinally for millennia, but the cannabinoid (CB) field exploded with the identification of its endogenous receptors and endocannabinoids (eCBs). In vitro experimentation established that eCBs alter synaptic plasticity at presynaptic nerve terminals; however, the characterization of the eCB system (ECS) in vivo remains incomplete. This study aimed to determine the mechanism of in vivo eCB-mediated hippocampal synaptic plasticity and to analyze the effects this plasticity had on spatial working memory (SWM). With in vivo recordings of field excitatory postsynaptic potentials (fEPSPs) in anesthetized mice and rats as well as pharmacological manipulation of the ECS and glutamate receptor antagonism, it was found that eCBs, both anandamide (AEA) and 2-arachnidonyl glycerol (2-AG), caused LTD at hippocampal CA3-CA1 synapses. Induction of eCB-LTD occurs via a sequential activation of cannabinoid type-1 receptor (CB1R) and NR2B-containing NMDA receptor (NR2BR) and is expressed through the endocytosis of AMPA receptors (AMPARs). Increased eCB tone also caused an impairment of SWM for over 24 hours in the Delayed Non-Match-To-Sample (DNMTS) T-maze. This study provides the first evidence that an acute administration of eCB degradative enzyme inhibitors not only produces an in vivo LTD at hippocampal CA3-CA1 synapses that requires CB1R, NR2BR, and AMPAR, but also impairs SWM, a phenomenon also caused by an acute injection of exogenous CBs.

Additional cognitive deficits, including impairments in spatial working memory and/or saccadic remapping processes, have recently been implicated in unilateral neglect – a neurological condition classically characterized as a disorder of attention. The interactions between saccadic remapping and three memory processes (position memory, object memory and object-location binding) were investigated in healthy young (n=27) and elderly (n=20) participants to establish a baseline of comparison for future use with neglect patients and to study the effects of aging on these processes. In a computerized task, participants were instructed to first detect a target, and then hold in memory either its position, identity or both over a delay period. Subsequently, participants were tested on their memory for that particular task. The saccadic remapping component was introduced at the onset of the delay period with the fixation cross shifting either to the left, or right, requiring participants to remap the visual array into either right or left space, or remaining in the centre of the screen (i.e., no remapping condition). In the position memory and object-location binding task, a consistent cost to memory performance was found when remapping right only for the young participants. Overall the elderly did not perform any of the tasks involving a position memory component as well as the young participants and showed spatial asymmetries in the target detection task. The lack of an effect of remapping in the elderly group may be due to a general decrement in performance. These results are discussed in terms of hemispheric asymmetries and cognitive theories of aging.

Additional cognitive deficits, including impairments in spatial working memory and/or saccadic remapping processes, have recently been implicated in unilateral neglect – a neurological condition classically characterized as a disorder of attention. The interactions between saccadic remapping and three memory processes (position memory, object memory and object-location binding) were investigated in healthy young (n=27) and elderly (n=20) participants to establish a baseline of comparison for future use with neglect patients and to study the effects of aging on these processes. In a computerized task, participants were instructed to first detect a target, and then hold in memory either its position, identity or both over a delay period. Subsequently, participants were tested on their memory for that particular task. The saccadic remapping component was introduced at the onset of the delay period with the fixation cross shifting either to the left, or right, requiring participants to remap the visual array into either right or left space, or remaining in the centre of the screen (i.e., no remapping condition). In the position memory and object-location binding task, a consistent cost to memory performance was found when remapping right only for the young participants. Overall the elderly did not perform any of the tasks involving a position memory component as well as the young participants and showed spatial asymmetries in the target detection task. The lack of an effect of remapping in the elderly group may be due to a general decrement in performance. These results are discussed in terms of hemispheric asymmetries and cognitive theories of aging.

In humans, damage to the mammillothalamic tract (MTT) as a result of localised strokes, tumours or alcohol abuse has consistently been implicated in the severe anterograde amnesia evident in these patients. This small neural pathway, which connects the mammillary bodies (MB) to the anterior thalamic nuclei (ATN), is thought to provide one important link in a larger extended hippocampal circuit involved in encoding and retrieval of episodic memory. Brain damage in clinical cases is, however, typically diffuse and contributions from additional sites of pathology cannot be ruled out. There are also inconsistencies within a limited animal literature on MTT lesions. The current study made MTT lesions in female rats and used multiple „episodic - like‟ memory tasks relevant to the proposed importance of this pathway. The project also intended to test whether enrichment reduces any impairments after MTT lesions. None of the lesions resulted in complete bilateral disconnection of the MTT, but many had moderate to large bilateral (n = 6) (81% to 50%), or unilateral MTT damage (n = 4). Rats with bilateral lesions were compared to controls (n = 14, including 4 other lesion rats in which no lesion occurred). The severe working memory deficit in the water maze expected for rats with MTT lesion was not found and only a slight deficit in reference memory in the water maze was observed (so enrichment was not implemented). Although none of the bilateral MTT lesions were complete, they are also often incomplete in clinical cases and previous research has shown that lesions to the ATN in excess of 50% are sufficient to induce severe behavioural deficits in rats. Therefore, if the MTT is critical to memory then substantial but not total bilateral disconnection should be sufficient to induce profound deficits in rats, at least on spatial working memory. Taken together these findings suggest a less crucial role for the MTT in memory than previously suggested. Future research needs to resolve the inconsistencies observed in the animal literature by repeating the present study, using larger MTT lesions and both male and female rats.

The term cognitive enhancers are substances that increase cognitive performance. The stimulant methylphenidate is commonly used as a medication for attention deficit hyperactive disorder and is highly popular as a cognitive enhancer. One of its theorized mechanisms of action is to enhance working memory. This systematic review aims to examine literature that tests the effect of methylphenidate on cognitive performance, specifically working memory, in healthy subjects. Following the PRISMA guidelines, a systematic search was conducted on Web of Science, Scopus, and Medline Ebsco on 1st March 2022. Articles were selected based on the predetermined eligibility criteria. Of the ten selected articles, three found a significant effect of methylphenidate on working memory, and one found a significant effect on spatial working memory. The studies produced varied results due to differential use of working memory tasks and methylphenidate dosage. Further studies on how methylphenidate affects working memory are needed.

Body schema is indispensable for sensorimotor control and learning, but it remains unclear whether it is associated with cognitive functions. Data from patients with spatial neglect support this view; yet observations in healthy participants are inconsistent. Here I conducted two sets of experiments examining influences of trunk position: the first probed attention and spatial working memory using a change detection task and a two-back task; the second used different versions of the Posner paradigm to examine whether head-on-trunk position governs disengagement of attention. In none of the experiments did I observe that trunk turns altered performance in the left versus right visual field in an ipsiversive fashion as reported in neglect. Nevertheless, I found that trunk-right position improved performance at eccentric locations of the visual field. The data are inconsistent with previous findings of head-on-trunk effects in normal participants. Further studies are required to clarify these discrepancies.

Body schema is indispensable for sensorimotor control and learning, but it remains unclear whether it is associated with cognitive functions. Data from patients with spatial neglect support this view; yet observations in healthy participants are inconsistent. Here I conducted two sets of experiments examining influences of trunk position: the first probed attention and spatial working memory using a change detection task and a two-back task; the second used different versions of the Posner paradigm to examine whether head-on-trunk position governs disengagement of attention. In none of the experiments did I observe that trunk turns altered performance in the left versus right visual field in an ipsiversive fashion as reported in neglect. Nevertheless, I found that trunk-right position improved performance at eccentric locations of the visual field. The data are inconsistent with previous findings of head-on-trunk effects in normal participants. Further studies are required to clarify these discrepancies.

Right parietal lesions often lead to neglect, in which patients fail to attend to leftward stimuli. Recent models of neglect suggest that, in addition to attentional impairments, patients demonstrate impairments of spatial remapping and/or spatial working memory (SWM). Although spatial remapping could be considered a kind of spatial memory process itself (i.e., updating remembered locations based on anticipated saccade outcomes), the two processes operate on very different time scales (milliseconds versus seconds). In the present study, the influence of saccadic and spatial remapping on SWM was examined in healthy individuals. An initial control condition, in which participants had to respond to a probe stimulus (i.e., “is the probe in the location previously occupied by the target?”) following a 1500 ms delay, was contrasted with conditions in which the fixation point moved (left, right, up, or down) at the onset of the delay. In a second version of the task, participants made covert shifts of attention at delay onset requiring covert spatial, rather than saccadic, remapping. In both tasks SWM performance was best when no remapping was required. Decrements in SWM were largest overall in the spatial remapping task, whereas for both saccadic and spatial remapping, a consistent cost was observed for remapping the target array into right visual space. Results are discussed in terms of hemispheric biases in attention and differences in performance for peripersonal versus extrapersonal space.

Right parietal lesions often lead to neglect, in which patients fail to attend to leftward stimuli. Recent models of neglect suggest that, in addition to attentional impairments, patients demonstrate impairments of spatial remapping and/or spatial working memory (SWM). Although spatial remapping could be considered a kind of spatial memory process itself (i.e., updating remembered locations based on anticipated saccade outcomes), the two processes operate on very different time scales (milliseconds versus seconds). In the present study, the influence of saccadic and spatial remapping on SWM was examined in healthy individuals. An initial control condition, in which participants had to respond to a probe stimulus (i.e., “is the probe in the location previously occupied by the target?”) following a 1500 ms delay, was contrasted with conditions in which the fixation point moved (left, right, up, or down) at the onset of the delay. In a second version of the task, participants made covert shifts of attention at delay onset requiring covert spatial, rather than saccadic, remapping. In both tasks SWM performance was best when no remapping was required. Decrements in SWM were largest overall in the spatial remapping task, whereas for both saccadic and spatial remapping, a consistent cost was observed for remapping the target array into right visual space. Results are discussed in terms of hemispheric biases in attention and differences in performance for peripersonal versus extrapersonal space.