scholarly journals Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jon Palacios-Filardo ◽  
Matt Udakis ◽  
Giles A. Brown ◽  
Benjamin G. Tehan ◽  
Miles S. Congreve ◽  
...  

AbstractAcetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, feedforward inhibition from entorhinal cortex exhibits greater depression than CA3 resulting in a selective enhancement of excitatory-inhibitory balance and CA1 activation by entorhinal inputs. Entorhinal and CA3 pathways engage different feedforward interneuron subpopulations and cholinergic modulation of presynaptic function is mediated differentially by muscarinic M3 and M4 receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation.

2020 ◽  
Author(s):  
Jon Palacios-Filardo ◽  
Matt Udakis ◽  
Giles A. Brown ◽  
Benjamin G. Tehan ◽  
Miles S. Congreve ◽  
...  

AbstractAcetylcholine release in the hippocampus plays a central role in the formation of new memory representations by facilitating synaptic plasticity. It is also proposed that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3, but this influential theory has not been directly tested. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, greater depression of feedforward inhibition from entorhinal cortex results in an overall enhancement of excitatory-inhibitory balance and CA1 activation. Underpinning the prioritisation of entorhinal inputs, entorhinal and CA3 pathways engage distinct feedforward interneuron subpopulations and depression is mediated differentially by presynaptic muscarinic M3 and M4 receptors respectively. These mechanisms enable acetylcholine to prioritise novel information inputs to CA1 during memory formation and suggest selective muscarinic targets for therapeutic intervention.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jon Palacios-Filardo ◽  
Matt Udakis ◽  
Giles A. Brown ◽  
Benjamin G. Tehan ◽  
Miles S. Congreve ◽  
...  

Author(s):  
Samantha Hughes ◽  
Tansu Celikel

From single-cell organisms to complex neural networks, all evolved to provide control solutions to generate context and goal-specific actions. Neural circuits performing sensorimotor computation to drive navigation employ inhibitory control as a gating mechanism, as they hierarchically transform (multi)sensory information into motor actions. Here, we focus on this literature to critically discuss the proposition that prominent inhibitory projections form sensorimotor circuits. After reviewing the neural circuits of navigation across various invertebrate species, we argue that with increased neural circuit complexity and the emergence of parallel computations inhibitory circuits acquire new functions. The contribution of inhibitory neurotransmission for navigation goes beyond shaping the communication that drives motor neurons, instead, include encoding of emergent sensorimotor representations. A mechanistic understanding of the neural circuits performing sensorimotor computations in invertebrates will unravel the minimum circuit requirements driving adaptive navigation.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Hemin Feng ◽  
Junfeng Su ◽  
Wei Fang ◽  
Xi Chen ◽  
Jufang He

Although fear memory formation is essential for survival and fear-related mental disorders, the neural circuitry and mechanism are incompletely understood. Here, we utilized trace fear conditioning to study the formation of trace fear memory in mice. We identified the entorhinal cortex (EC) as a critical component of sensory signaling to the amygdala. We adopted both loss-of-function and gain-of-function experiments to demonstrate that release of the cholecystokinin (CCK) from the EC is required for trace fear memory formation. We discovered that CCK-positive neurons project from the EC to the lateral nuclei of the amygdala (LA), and inhibition of CCK-dependent signaling in the EC prevented long-term potentiation of the auditory response in the LA and formation of trace fear memory. In summary, high-frequency activation of EC neurons triggers the release of CCK in their projection terminals in the LA, potentiating auditory response in LA neurons. The neural plasticity in the LA leads to trace fear memory formation.


2019 ◽  
Author(s):  
David A. Tovar ◽  
Micah M. Murray ◽  
Mark T. Wallace

AbstractObjects are the fundamental building blocks of how we create a representation of the external world. One major distinction amongst objects is between those that are animate versus inanimate. Many objects are specified by more than a single sense, yet the nature by which multisensory objects are represented by the brain remains poorly understood. Using representational similarity analysis of human EEG signals, we show enhanced encoding of audiovisual objects when compared to their corresponding visual and auditory objects. Surprisingly, we discovered the often-found processing advantages for animate objects was not evident in a multisensory context due to greater neural enhancement of inanimate objects—the more weakly encoded objects under unisensory conditions. Further analysis showed that the selective enhancement of inanimate audiovisual objects corresponded with an increase in shared representations across brain areas, suggesting that neural enhancement was mediated by multisensory integration. Moreover, a distance-to-bound analysis provided critical links between neural findings and behavior. Improvements in neural decoding at the individual exemplar level for audiovisual inanimate objects predicted reaction time differences between multisensory and unisensory presentations during a go/no-go animate categorization task. Interestingly, links between neural activity and behavioral measures were most prominent 100 to 200ms and 350 to 500ms after stimulus presentation, corresponding to time periods associated with sensory evidence accumulation and decision-making, respectively. Collectively, these findings provide key insights into a fundamental process the brain uses to maximize information it captures across sensory systems to perform object recognition.Significance StatementOur world is filled with an ever-changing milieu of sensory information that we are able to seamlessly transform into meaningful perceptual experience. We accomplish this feat by combining different features from our senses to construct objects. However, despite the fact that our senses do not work in isolation but rather in concert with each other, little is known about how the brain combines the senses together to form object representations. Here, we used EEG and machine learning to study how the brain processes auditory, visual, and audiovisual objects. Surprisingly, we found that non-living objects, the objects which were more difficult to process with one sense alone, benefited the most from engaging multiple senses.


2020 ◽  
Vol 117 (39) ◽  
pp. 24590-24598
Author(s):  
Freek van Ede ◽  
Alexander G. Board ◽  
Anna C. Nobre

Adaptive behavior relies on the selection of relevant sensory information from both the external environment and internal memory representations. In understanding external selection, a classic distinction is made between voluntary (goal-directed) and involuntary (stimulus-driven) guidance of attention. We have developed a task—the anti-retrocue task—to separate and examine voluntary and involuntary guidance of attention to internal representations in visual working memory. We show that both voluntary and involuntary factors influence memory performance but do so in distinct ways. Moreover, by tracking gaze biases linked to attentional focusing in memory, we provide direct evidence for an involuntary “retro-capture” effect whereby external stimuli involuntarily trigger the selection of feature-matching internal representations. We show that stimulus-driven and goal-directed influences compete for selection in memory, and that the balance of this competition—as reflected in oculomotor signatures of internal attention—predicts the quality of ensuing memory-guided behavior. Thus, goal-directed and stimulus-driven factors together determine the fate not only of perception, but also of internal representations in working memory.


1997 ◽  
Vol 78 (2) ◽  
pp. 1062-1081 ◽  
Author(s):  
Wendy A. Suzuki ◽  
Earl K. Miller ◽  
Robert Desimone

Suzuki, Wendy A., Earl K. Miller, and Robert Desimone. Object and place memory in the macaque entorhinal cortex. J. Neurophysiol. 78: 1062–1081, 1997. Lesions of the entorhinal cortex in humans, monkeys, and rats impair memory for a variety of kinds of information, including memory for objects and places. To begin to understand the contribution of entorhinal cells to different forms of memory, responses of entorhinal cells were recorded as monkeys performed either an object or place memory task. The object memory task was a variation of delayed matching to sample. A sample picture was presented at the start of the trial, followed by a variable sequence of zero to four test pictures, ending with a repetition of the sample (i.e., a match). The place memory task was a variation of delayed matching to place. In this task, a cue stimulus was presented at a variable sequence of one to four “places” on a computer screen, ending with a repetition of one of the previously shown places (i.e., a match). For both tasks, the animals were rewarded for releasing a bar to the match. To solve these tasks, the monkey must 1) discriminate the stimuli, 2) maintain a memory of the appropriate stimuli during the course of the trial, and 3) evaluate whether a test stimulus matches previously presented stimuli. The responses of entorhinal cortex neurons were consistent with a role in all three of these processes in both tasks. We found that 47% and 55% of the visually responsive entorhinal cells responded selectively to the different objects or places presented during the object or place task, respectively. Similar to previous findings in prefrontal but not perirhinal cortex on the object task, some entorhinal cells had sample-specific delay activity that was maintained throughout all of the delay intervals in the sequence. For the place task, some cells had location-specific maintained activity in the delay immediately following a specific cue location. In addition, 59% and 22% of the visually responsive cells recorded during the object and place task, respectively, responded differently to the test stimuli according to whether they were matching or nonmatching to the stimuli held in memory. Responses of some cells were enhanced to matching stimuli, whereas others were suppressed. This suppression or enhancement typically occurred well before the animals' behavioral response, suggesting that this information could be used to perform the task. These results indicate that entorhinal cells receive sensory information about both objects and spatial locations and that their activity carries information about objects and locations held in short-term memory.


2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Lia R. M. Bevilaqua ◽  
Janine I. Rossato ◽  
Juliana S. Bonini ◽  
Jociane C. Myskiw ◽  
Julia R. Clarke ◽  
...  

The entorhinal cortex is perhaps the area of the brain in which neurofibrillary tangles and amyloid plaques are first detectable in old age with or without mild cognitive impairment, and very particularly in Alzheimer's disease. It plays a key role in memory formation, retrieval, and extinction, as part of circuits that include the hippocampus, the amygdaloid nucleus, and several regions of the neocortex, in particular of the prefrontal cortex. Lesions or biochemical impairments of the entorhinal cortex hinder extinction. Microinfusion experiments have shown that glutamate NMDA receptors, calcium and calmodulin-dependent protein kinase II, and protein synthesis in the entorhinal cortex are involved in and required for extinction. Aging also hinders extinction; it is possible that its effect may be in part mediated by the entorhinal cortex.


1993 ◽  
Vol 69 (6) ◽  
pp. 1789-1796 ◽  
Author(s):  
A. M. Gordon ◽  
G. Westling ◽  
K. J. Cole ◽  
R. S. Johansson

1. While subjects lifted a variety of commonly handled objects of different shapes, weights, and densities, the isometric vertical lifting force opposing the object's weight was recorded from an analog weight scale, which was instrumented with high-stiffness strain gauge transducers. 2. The force output was scaled differently for the various objects from the first lift, before sensory information related to the object's weight was available. The force output was successfully specified from information in memory related to the weight of common objects, because only small changes in the force-rate profiles occurred across 10 consecutive lifts. This information was retrieved during a process related to visual identification of the target object. 3. The amount of practice necessary to appropriately scale the vertical lifting and grip (pinch) force was also studied when novel objects (equipped with force transducers at the grip surfaces) of different densities were encountered. The mass of a test object that subjects had not seen previously was adjusted to either 300 or 1,000 g by inserting an appropriate mass in the object's base without altering its appearance. This resulted in either a density that was in the range of most common objects (1.2 kg/l) or a density that was unusually high (4.0 kg/l). 4. Low vertical-lifting and grip-force rates were used initially with the high-density object, as if a lighter object had been expected. However, within the first few trials, the duration of the loading phase (period of isometric force increase before lift-off) was reduced by nearly 50% and the employed force-rate profiles were targeted for the weight of the object.(ABSTRACT TRUNCATED AT 250 WORDS)


2021 ◽  
pp. 1-14
Author(s):  
Saana M. Korkki ◽  
Franziska R. Richter ◽  
Jon S. Simons

Abstract Our recollections of past experiences can vary in both the number of specific event details accessible from memory and the precision with which such details are reconstructed. Prior neuroimaging evidence suggests the success and precision of episodic recollection to rely on distinct neural substrates during memory retrieval. In contrast, the specific encoding mechanisms supporting later memory precision, and whether they differ from those underlying successful memory formation in general, are currently unknown. Here, we combined continuous measures of memory retrieval with model-based analyses of behavioral and neuroimaging data to tease apart the encoding correlates of successful memory formation and mnemonic precision. In the MRI scanner, participants encoded object-scene displays and later reconstructed features of studied objects using a continuous scale. We observed overlapping encoding activity in inferior prefrontal and posterior perceptual regions to predict both which object features were later remembered versus forgotten and the precision with which they were reconstructed from memory. In contrast, hippocampal encoding activity significantly predicted the precision, but not overall success, of subsequent memory retrieval. The current results align with theoretical accounts proposing the hippocampus to be critical for representation of high-fidelity associative information and suggest a contribution of shared cortical encoding mechanisms to the formation of both accessible and precise memory representations.


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