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      Maintenance of persistent activity in a frontal thalamocortical loop

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          Abstract

          Persistent neural activity maintains information bridging past and future events. Models of persistent activity often invoke reverberations within local cortical circuits, but long-range circuits could also contribute. Neurons in mouse anterior lateral motor cortex (ALM) show selective persistent activity that instructs future actions. ALM is connected bi-directionally with parts of the thalamus, including the ventral medial and ventral anterior-lateral nuclei. We recorded spikes from ALM and thalamus during tactile discrimination with a delayed directional response. Similar to ALM neurons, thalamic neurons exhibited selective persistent delay activity that predicted movement direction. Unilateral photoinhibition of delay activity in ALM or thalamus produced contralesional neglect. Photoinhibition of thalamus caused a short-latency and near total collapse of ALM activity. Similarly, photoinhibition of ALM diminished thalamic activity. Our results reveal thalamus as a circuit hub in motor preparation and suggest that persistent activity requires reciprocal excitation across multiple brain areas.

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          Most cited references54

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          A mesoscale connectome of the mouse brain.

          Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.
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            Cellular basis of working memory

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              Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex.

              1. An oculomotor delayed-response task was used to examine the spatial memory functions of neurons in primate prefrontal cortex. Monkeys were trained to fixate a central spot during a brief presentation (0.5 s) of a peripheral cue and throughout a subsequent delay period (1-6 s), and then, upon the extinction of the fixation target, to make a saccadic eye movement to where the cue had been presented. Cues were usually presented in one of eight different locations separated by 45 degrees. This task thus requires monkeys to direct their gaze to the location of a remembered visual cue, controls the retinal coordinates of the visual cues, controls the monkey's oculomotor behavior during the delay period, and also allows precise measurement of the timing and direction of the relevant behavioral responses. 2. Recordings were obtained from 288 neurons in the prefrontal cortex within and surrounding the principal sulcus (PS) while monkeys performed this task. An additional 31 neurons in the frontal eye fields (FEF) region within and near the anterior bank of the arcuate sulcus were also studied. 3. Of the 288 PS neurons, 170 exhibited task-related activity during at least one phase of this task and, of these, 87 showed significant excitation or inhibition of activity during the delay period relative to activity during the intertrial interval. 4. Delay period activity was classified as directional for 79% of these 87 neurons in that significant responses only occurred following cues located over a certain range of visual field directions and were weak or absent for other cue directions. The remaining 21% were omnidirectional, i.e., showed comparable delay period activity for all visual field locations tested. Directional preferences, or lack thereof, were maintained across different delay intervals (1-6 s). 5. For 50 of the 87 PS neurons, activity during the delay period was significantly elevated above the neuron's spontaneous rate for at least one cue location; for the remaining 37 neurons only inhibitory delay period activity was seen. Nearly all (92%) neurons with excitatory delay period activity were directional and few (8%) were omnidirectional. Most (62%) neurons with purely inhibitory delay period activity were directional, but a substantial minority (38%) was omnidirectional. 6. Fifteen of the neurons with excitatory directional delay period activity also had significant inhibitory delay period activity for other cue directions. These inhibitory responses were usually strongest for, or centered about, cue directions roughly opposite those optimal for excitatory responses.(ABSTRACT TRUNCATED AT 400 WORDS)
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                4 April 2017
                03 May 2017
                11 May 2017
                23 March 2019
                : 545
                : 7653
                : 181-186
                Affiliations
                [1 ]Janelia Research Campus, HHMI, Ashburn VA 20147
                [3 ]Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, MD 20892
                Author notes
                Correspondence: Karel Svoboda, Janelia Research Campus, HHMI, 19700 Helix Drive, Ashburn, VA 20147, svobodak@ 123456janelia.hhmi.org
                [2]

                These authors contributed equally to this work

                Article
                HHMIMS865428
                10.1038/nature22324
                6431254
                28467817
                09513643-e385-4511-b494-ffe1551b7980

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