Persistent activity underlying short-term memory encodes sensory information or instructs specific future movement and, consequently, has a crucial role in cognition. Despite extensive study, how the same set of neurons respond differentially to form selective persistent activity remains unknown. Here, we report that the cortico-basal ganglia-thalamo-cortical (CBTC) circuit supports the formation of selective persistent activity in mice. Optogenetic activation or inactivation of the basal ganglia output nucleus substantia nigra pars reticulata (SNr)-to-thalamus pathway biased future licking choice, without affecting licking execution. This perturbation differentially affected persistent activity in the frontal cortex and selectively modulated neural trajectory that encodes one choice but not the other. Recording showed that SNr neurons had selective persistent activity distributed across SNr, but with a hotspot in the mediolateral region. Optogenetic inactivation of the frontal cortex also differentially affected persistent activity in the SNr. Together, these results reveal a CBTC channel functioning to produce selective persistent activity underlying short-term memory.

Buffer accounts of verbal short-term memory (STM) assume dedicated buffers for maintaining different types of information (e.g., phonological, visual) whereas embedded processes accounts argue against the existence of buffers and claim that STM consists of the activated portion of long-term memory (LTM). We addressed this debate by determining whether STM recruits the same neural substrate as LTM, or whether additional regions are involved in short-term storage. Using fMRI with representational similarity analysis (RSA), we examined the representational correspondence of multi-voxel neural activation patterns with the theoretical predictions for the maintenance of both phonological and semantic codes in STM. We found that during the delay period of a phonological STM task, phonological representations could be decoded in the left supramarginal gyrus (SMG) but not the superior temporal gyrus (STG), a speech processing region, for word stimuli. Whereas the pattern in the SMG was specific to phonology, a different region in the left angular gyrus showed RSA decoding evidence for the retention of either phonological or semantic codes, depending on the task context. Taken together, the results provide clear support for a dedicated buffer account of phonological STM, although evidence for a semantic buffer is equivocal.

Learning of adaptive behaviors requires the refinement of coordinated activity across multiple brain regions. However, how neural communications develop during learning remains poorly understood. Here, using two-photon calcium imaging, we simultaneously recorded the activity of layer 2/3 excitatory neurons in eight regions of the mouse dorsal cortex during learning of a delayed-response task. Across learning, while global functional connectivity became sparser, there emerged a subnetwork comprising of neurons in the anterior lateral motor cortex (ALM) and posterior parietal cortex (PPC). Neurons in this subnetwork shared a similar choice code during action preparation and formed recurrent functional connectivity across learning. Suppression of PPC activity disrupted choice selectivity in ALM and impaired task performance. Recurrent neural networks reconstructed from ALM activity revealed that PPC-ALM interactions rendered choice-related attractor dynamics more stable. Thus, learning constructs cortical network motifs by recruiting specific inter-areal communication channels to promote efficient and robust sensorimotor transformation.

The consolidation of new memories into long-lasting memories is multistage process characterized by distinct temporal dynamics. However, our understanding on the initial stage of transformation of labile memory of recent experience into stable memory remains elusive. Here, with the use of rats and mice overexpressing a memory enhancer called regulator of G protein signaling 14 of 414 amino acids (RGS14414 ) as a tool, we show that the expression of RGS14414 in male rats' perirhinal cortex (PRh), which is a brain area crucial for object recognition memory (ORM), enhanced the ORM to the extent that it caused the conversion of labile short-term ORM (ST-ORM) expected to last for 40 min into stable long-term ORM (LT-ORM) traceable after a delay of 24 hr, and that the temporal window of 40 to 60 min after object exposure not only was key for this conversion but also was the time frame when a surge in 14-3-3ζ protein was observed. A knockdown of 14-3-3ζ gene abrogated both the increase in 14-3-3ζ protein and the formation of LT-ORM. Furthermore, this 14-3-3ζ upregulation increased brain-derived growth factor (BDNF) levels in the time frame of 60 min and 24 hr and 14-3-3ζ knockdown decreased the BDNF levels, and a deletion of BDNF gene produced loss in mice ability to form LT-ORM. Thus, within 60 min of object exposure, 14-3-3ζ facilitated the conversion of labile ORM into stable ORM, whereas beyond the 60 min, it mediated the consolidation of the stable memory into long-lasting ORM by regulating BDNF signaling.

Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling - a slow process usually associated with the maintenance of activity homeostasis - combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes.

The goal of the present study was to examine the extent to which working memory supports the maintenance of object locations during active spatial navigation. Participants were required to navigate a virtual environment and to encode the location of a target object. In the subsequent maintenance period they performed one of three secondary tasks that were designed to selectively load visual, verbal or spatial working memory subsystems. Thereafter participants re-entered the environment and navigated back to the remembered location of the target. We found that while navigation performance in participants with high navigational ability was impaired only by the spatial secondary task, navigation performance in participants with poor navigational ability was impaired equally by spatial and verbal secondary tasks. The visual secondary task had no effect on navigation performance. Our results extend current knowledge by showing that the differential engagement of working memory subsystems is determined by navigational ability.

There is evidence that exposure to stressors in adolescence leads to lasting deficits on hippocampal-dependent tasks, but whether medial prefrontal cortical function is also impaired is unknown. We previously found that rats exposed to social instability stress in adolescence (SS; daily 1h isolation and subsequent change of cage partner between postnatal days 30 and 45) had impaired memory performance on a Spatial Object Location test and in memory for fear conditioning context, tasks that depend on the integrity of the hippocampus. Here we investigated whether impaired performance would be evident after adolescent SS in male rats on a different test of hippocampal function, spatial learning and memory in the Morris water maze (MWM) and on a working memory task for which performance depends on the integrity of the medial prefrontal cortex, the Delayed Alternation task (DAT). During MWM testing, SS rats showed greater improvements in performance across trials within days compared to control (CTL) rats, but showed less retention of learning between days (48 h) compared to CTL rats. Similarly, SS rats had impaired long-term memory in the Spatial Object Location test after a long delay (240 min), but not after shorter delays (15 or 60 min) compared to CTL rats. No group differences were observed on the DAT, which assessed working memory across brief delays (5-90 s). Thus, deficits in memory performance after chronic social stress in adolescence may be limited to long-term memory.

Spatial information plays an important role in how we remember. In general, there are two (non mutually exclusive) views regarding the role that space plays in memory. One view is that objects overlapping in space interfere with each other in memory. For example, objects presented in the same location (at different points in time) are more frequently confused with one another than objects that are not. Another view is that spatial information can 'bootstrap' other kinds of information. For example, remembering a phone number is easier one can see the arrangement of a keypad. Here, building on both perspectives, we test the hypothesis that task-irrelevant spatial structure (i.e., objects appearing in stable locations over repeated iterations) improves working memory. Across 7 experiments, we demonstrate that (1) irrelevant spatial structure improves memory for sequences of objects; (2) this effect does not depend on long-term spatial associations; (3) this effect is unique to space (as opposed to features like color); and (4) spatial structure can be teased apart from spatial interference, and the former drives memory improvement. We discuss how these findings relate to and challenge 'spatial interference' accounts as well as 'visuospatial bootstrapping'.

Recent evidence suggests that the monkey's short-term memory in audition depends on a passively retained sensory trace as opposed to a trace reactivated from long-term memory for use in working memory. Reliance on a passive sensory trace could render memory particularly susceptible to confusion between sounds that are similar in some acoustic dimension. If so, then in delayed matching-to-sample, the monkey's performance should be predicted by the similarity in the salient acoustic dimension between the sample and subsequent test stimulus, even at very short delays. To test this prediction and isolate the acoustic features relevant to short-term memory, we examined the pattern of errors made by two rhesus monkeys performing a serial, auditory delayed match-to-sample task with interstimulus intervals of 1 s. The analysis revealed that false-alarm errors did indeed result from similarity-based confusion between the sample and the subsequent nonmatch stimuli. Manipulation of the stimuli showed that removal of spectral cues was more disruptive to matching behavior than removal of temporal cues. In addition, the effect of acoustic similarity on false-alarm response was stronger at the first nonmatch stimulus than at the second one. This pattern of errors would be expected if the first nonmatch stimulus overwrote the sample's trace, and suggests that the passively retained trace is not only vulnerable to similarity-based confusion but is also highly susceptible to overwriting.

Scopolamine is a nonselective muscarinic cholinergic receptor antagonist, which induces impairment of learning ability and memory function. Exercise is known to ameliorate brain disturbance induced by brain injuries. In the present study, we investigated the effect of treadmill exercise on short-term memory in relation to acetylcholinesterase (AChE) expression in the hippocampus, using a scopolamine-induced amnesia model in mice.

Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high risk of developing Parkinson's disease with cognitive deficit. We examined whether visual short-term memory impairments, long associated with patients with Parkinson's disease, are also present in GBA-positive individuals-both with and without Parkinson's disease. Precision of visual working memory was measured using a serial order task in which participants observed four bars, each of a different colour and orientation, presented sequentially at screen centre. Afterwards, they were asked to adjust a coloured probe bar's orientation to match the orientation of the bar of the same colour in the sequence. An additional attentional 'filtering' condition tested patients' ability to selectively encode one of the four bars while ignoring the others. A sensorimotor task using the same stimuli controlled for perceptual and motor factors. There was a significant deficit in memory precision in GBA-positive individuals-with or without Parkinson's disease-as well as GBA-negative patients with Parkinson's disease, compared to healthy controls. Worst recall was observed in GBA-positive cases with Parkinson's disease. Although all groups were impaired in visual short-term memory, there was a double dissociation between sources of error associated with GBA mutation and Parkinson's disease. The deficit observed in GBA-positive individuals, regardless of whether they had Parkinson's disease, was explained by a systematic increase in interference from features of other items in memory: misbinding errors. In contrast, impairments in patients with Parkinson's disease, regardless of GBA status, was explained by increased random responses. Individuals who were GBA-positive and also had Parkinson's disease suffered from both types of error, demonstrating the worst performance. These findings provide evidence for dissociable signature deficits within the domain of visual short-term memory associated with GBA mutation and with Parkinson's disease. Identification of the specific pattern of cognitive impairment in GBA mutation versus Parkinson's disease is potentially important as it might help to identify individuals at risk of developing Parkinson's disease.

Recent research has suggested that short-term memory (STM) can be partitioned into three distinct states. By this model, a single item is held in the focus of attention making it available for immediate processing (focus of attention), a capacity-limited set of additional items is actively maintained for future processing (direct access region), and other recently presented information is passively active, but can nevertheless influence ongoing cognition (activated portion of long-term memory). While there is both behavioral and neural support for this 3-state model in verbal STM, it is unclear whether the model generalizes to non-verbal STM. Here, we tested a 3-state model of visual STM using fMRI. We found a triple dissociation of regions involved in the access of each hypothesized state. The inferior parietal cortex mediated access to the focus of attention, the medial temporal lobe (MTL) including the hippocampus mediated access to the direct access region, and the left ventrolateral prefrontal cortex (VLPFC) mediated access to the activated portion of long-term memory. Direct comparison with previously collected verbal STM data revealed overlapping neural activations involved in the access of each state across different forms of content suggesting that mechanisms of access are domain general. These data support a 3-state model of STM.

The proper development and function of neuronal circuits rely on a tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission, and disrupting this balance can cause neurodevelopmental disorders, for example, schizophrenia. MicroRNA-dependent gene regulation in pyramidal neurons is important for excitatory synaptic function and cognition, but its role in inhibitory interneurons is poorly understood. Here, we identify miR138-5p as a regulator of short-term memory and inhibitory synaptic transmission in the mouse hippocampus. Sponge-mediated miR138-5p inactivation specifically in mouse parvalbumin (PV)-expressing interneurons impairs spatial recognition memory and enhances GABAergic synaptic input onto pyramidal neurons. Cellular and behavioral phenotypes associated with miR138-5p inactivation are paralleled by an upregulation of the schizophrenia (SCZ)-associated Erbb4, which we validated as a direct miR138-5p target gene. Our findings suggest that miR138-5p is a critical regulator of PV interneuron function in mice, with implications for cognition and SCZ. More generally, they provide evidence that microRNAs orchestrate neural circuit development by fine-tuning both excitatory and inhibitory synaptic transmission.

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by deterioration in motor, oculomotor and cognitive function. A key clinical feature of PSP is the progressive paralysis of eye movements, most notably for vertical saccades. These oculomotor signs can be subtle, however, and PSP is often misdiagnosed as Parkinson's disease (PD), in its early stages. Although some of the clinical features of PD and PSP overlap, they are distinct disorders with differing underlying pathological processes, responses to treatment and prognoses. One key difference lies in the effects the diseases have on cognition. The oculomotor system is tightly linked to cognitive processes such as spatial attention and spatial short-term memory (sSTM), and previous studies have suggested that PSP and PD experience different deficits in these domains. We therefore hypothesised that people with PSP (N = 15) would experience problems with attention (assessed with feature and conjunction visual search tasks) and sSTM (assessed with the Corsi blocks task) compared to people with PD (N = 16) and Age Matched Controls (N = 15). As predicted, feature and conjunction search were sgnificantly slower in the PSP group compared to the other groups, and this deficit was significantly worse for feature compared to conjunction search. The PD group did not differ from AMC on feature search but were significantly impaired on the conjunction search. The PSP group also had a pronounced vertical sSTM impairment that was not present in PD or AMC groups. It is argued that PSP is associated with specific impairment of visuospatial cognition which is caused by degeneration of the oculomotor structures that support exogenous spatial attention, consistent with oculomotor theories of spatial attention and memory.

Limits to the capacity of visual short-term memory (VSTM) indicate a maximum storage of only 3 or 4 items. Recently, it has been suggested that activity in a specific part of the brain, the posterior parietal cortex (PPC), is correlated with behavioral estimates of VSTM capacity and might reflect a capacity-limited store. In three experiments that varied the delay period and the stimuli to be stored, we found dissociations between functional magnetic resonance imaging (fMRI) activity in PPC and behavioral measures of capacity. When the delay length increased, fMRI activity in this area increased with memory load beyond the behaviorally determined limits of capacity. The results suggest that activity in PPC may reflect the attentional demands of short-term memory rehearsal processes rather than capacity limitations, and imply that a larger number of items than that determined by behavioral measures of capacity may be rehearsed during STM tasks. This account is consistent with the role of PPC in attentional processes and with the close correlation between brain areas that are involved in attention and those that mediate STM.

Previous studies suggested that ERP component contralateral delay activity (CDA) tracks the number of objects containing identity information stored in visual short term memory (VSTM). Later MEG and fMRI studies implied that its neural source lays in superior IPS. However, since the memorized stimuli in previous studies were displayed in distinct spatial locations, hence possibly CDA tracks the object-location information instead. Moreover, a recent study implied the activation in superior IPS reflected the location load. The current research thus explored whether CDA tracks the object-location load or the object-identity load, and its neural sources. Participants were asked to remember one color, four identical colors or four distinct colors. The four-identical-color condition was the critical one because it contains the same amount of identity information as that of one color while the same amount of location information as that of four distinct colors. To ensure the participants indeed selected four colors in the four-identical-color condition, we also split the participants into two groups (low- vs. high-capacity), analyzed late positive component (LPC) in the prefrontal area, and collected participant's subjective-report. Our results revealed that most of the participants selected four identical colors. Moreover, regardless of capacity-group, there was no difference on CDA between one color and four identical colors yet both were lower than 4 distinct colors. Besides, the source of CDA was located in the superior parietal lobule, which is very close to the superior IPS. These results support the statement that CDA tracks the object identity information in VSTM.

Network functioning during cognitive tasks is of major interest in Alzheimer's disease (AD). Cognitive functioning in AD includes variable performance in short-term memory (STM). In most studies, the verbal STM functioning in AD patients has been interpreted within the phonological loop subsystem of Baddeley's working memory model. An alternative account considers that domain-general attentional processes explain the involvement of frontoparietal networks in verbal STM beside the functioning of modality-specific subsystems. In this study, we assessed the functional integrity of the dorsal attention network (involved in task-related attention) and the ventral attention network (involved in stimulus-driven attention) by varying attentional control demands in a STM task. Thirty-five AD patients and twenty controls in the seventies performed an fMRI STM task. Variation in load (five versus two items) allowed the dorsal (DAN) and ventral attention networks (VAN) to be studied. ANOVA revealed that performance decreased with increased load in both groups. AD patients performed slightly worse than controls, but accuracy remained above 70% in all patients. Statistical analysis of fMRI brain images revealed DAN activation for high load in both groups. There was no between-group difference or common activation for low compared to high load conditions. Psychophysiological interaction showed a negative relationship between the DAN and the VAN for high versus low load conditions in patients. In conclusion, the DAN remained activated and connected to the VAN in mild AD patients who succeeded in performing an fMRI verbal STM task. DAN was necessary for the task, but not sufficient to reach normal performance. Slightly lower performance in early AD patients compared to controls might be related to maintained bottom-up attention to distractors, to decrease in executive functions, to impaired phonological processing or to reduced capacity in serial order processing.

To investigate the involvement of oxytocin in their short-term lasting olfactory memory performance, adult female Wistar rats (n = 12) were tested for their juvenile discrimination abilities. As measured by their exploratory behavior towards juveniles, the adult rats were able to discriminate between a previously exposed juvenile and a novel one as long as the interval between the two exposures was less than 180 min. This ability was maintained across all days of the estrous cycle and was unaffected by intracerebroventricular administration of synthetic oxytocin (1 ng/5 microl Ringer's solution) or Ringer's solution immediately after the first exposure. However, treatment with the oxytocin receptor antagonist des-Gly-NH2 d(CH2)5[Tyr(Me)2Thr4]OVT interfered with the ability to establish this kind of olfactory memory although the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP (100 ng/5 microl each) via the same route did not. This suggests that within a narrow range of concentrations endogenous oxytocin, but not vasopressin, is critically involved in short-term olfactory memory for juvenile conspecifics in female rats. These data are discussed in the light of sexual dimorphic brain development.

Aim-The purpose of this study was to assess the effect of the Burpee exercise on the endurance and short-term memory of adolescents aged 15-16 years. Methods-The experiment was performed in a coeducational school in Kirov (Russia). The four-month study involved 52 adolescents of both genders. During the study period, 30 physical education lessons were held in each class. Adolescents from the control group were involved in a typical program (also aimed at improving endurance), and adolescents from the experimental group additionally performed the Burpee exercise. Endurance in adolescents was assessed by means of an "all-out" Running 2000 m test, and short-term memory was assessed by means of the Jacobs test (tests were performed before and after the programs). Results-An analysis of variance revealed an interaction effect (F = 28.733, ηp2 = 0.578 and p < 0.001, and F = 104.353, ηp2 = 0.676 and p < 0.001 for the Running 2000 m test and the Jacobs test, respectively). The control group improved by 1.9% (p > 0.05) in the Running 2000 m and by 5.5% (p > 0.05) in the Jacobs test. In the experimental group, both improved significantly by 8.6% (p < 0.05) in the Running 2000 m test and by 26.0% (p < 0.05) in the Jacobs test. Conclusion-The Burpee exercise could be included in physical education classes to improve endurance and short-term memory in 15-16-year-old.

The current study examined the phonological and semantic contributions to the verbal short-term memory (VSTM) deficit in Down syndrome (DS) by experimentally manipulating the phonological and semantic demands of VSTM tasks. The performance of 18 individuals with DS (ages 11-25) and 18 typically developing children (ages 3-10) matched pairwise on receptive vocabulary and gender was compared on four VSTM tasks, two tapping phonological VSTM (phonological similarity, nonword discrimination) and two tapping semantic VSTM (semantic category, semantic proactive interference). Group by condition interactions were found on the two phonological VSTM tasks (suggesting less sensitivity to the phonological qualities of words in DS), but not on the two semantic VSTM tasks. These findings suggest that a phonological weakness contributes to the VSTM deficit in DS. These results are discussed in relation to the DS neuropsychological and neuroanatomical phenotype.