シンポジウム
18 Developmental Integration of Long-range Projection to Cortical Microcircuit
座長：森下 博文（Friedman Brain Institute, Department of Psychiatry, Icahn School ofMedicine at Mount Sinai, New York, USA）・Ibrahim Marosh Leena Ali（KAUST, SaudiArabia） |
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| 2022年6月30日 16:10～16:34 ラグナガーデンホテル 羽衣：西 第10会場
1S10e-01
Precise long-range circuit organization in the neocortex
*Song-Hai Shi(1)
1. IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing, China
Keyword: neocortex, long-range projection, neural circuit, disease
The ability of the neocortex to command higher-order brain functions depends on the assembly and operation of intricate neural circuitries. Besides local microcircuits, long-range bottom-up and top-down projections between the sensory area and the frontal area are crucial for the operation of the neocortex and complex behavioral control. However, the precise organization of these long-range circuits remains poorly understood. Recently, we specifically identified the presynaptic input neurons to individual excitatory neuron clones as a unit that constitutes functional microcircuits in the mouse sensory cortex. Interestingly, the long-range input neurons in the frontal but not contralateral sensory area are spatially organized into discrete vertical clusters and preferentially form synapses with each other over nearby non-input neurons. In this presentation, I will discuss the highly precise long-range microcircuit-to-microcircuit communication in the neocortex under normal and disease conditions. | | 2022年6月30日 16:34～16:58 ラグナガーデンホテル 羽衣：西 第10会場
1S10e-02
Developmental integration of clonally-related cortical neural assemblies
*Etsuko Tarusawa(1)
1. Grad Sch Front Biosci, Univ of Osaka, Osaka, Japan
Keyword: clustered protocadherin, cell lineage, activity-dependent neural connections, barrel cortex
The specificity of neural connections in the sensory cortex is fundamental for the proper processing of sensory information. We previously have shown that high reciprocal connectivity is established between clonal cortical neurons and the establishment is regulated by clustered protocadherins in mouse barrel cortex. In this study, we analyzed the effect of sensory deprivation on the establishment of the cell-lineage-dependent reciprocal connectivity. To visualize clonal neurons, we generated chimeric mice by injecting a single induced pluripotent stem cell (iPS cell) marked with GFP into blastocysts. We conducted dual whole-cell recordings from GFP-positive excitatory neuron pairs (presumed clonal pairs) or GFP-positive and negative excitatory neuron pairs (non-clonal pairs) within a layer 4 barrel in acute cortical slices prepared from the chimeric mice. In naïve chimeric mice at postnatal day 9 (P9) to P11, almost all connected neuron pairs showed one-way connections in both clonal and non-clonal neuron pairs. After that, high reciprocal connectivity in clonal neuron pairs was established by two sequential processes, an initial formation of reciprocal connections from P9-11 to P13-16, and a selective elimination of one-way connections from P13-16 to P18-20. As a result, 83% of connected neuron pairs showed reciprocal connections. This high reciprocity was not observed in non-clonal neuron pairs.To reveal the influence of sensory deprivation on the development of high reciprocal connectivity, whisker trimming was performed on the chimeric mice from P13 to the day before recording. In clonal neuron pairs after whisker-trimming, the formation of reciprocal connections at P15-16 was strongly suppressed and the lower reciprocity was kept at P18-20. The elimination of one-way connections from P15-16 to P18-20 was also prevented by the whisker trimming. Surprisingly, the effect of sensory deprivation on the neural connections was not observed in non-clonal neuron pairs, suggesting that cell-lineage-specific neural connections are selectively modified by sensory experience. Our previous and current findings suggest that the sensory inputs and clustered protocadherins are required for the establishment of reciprocal connections between clonal neurons, and further investigations into the signaling pathways to link neural activity and clustered protocadherins may shed light on the mechanisms underlying cell-lineage-dependent connection specificity in neocortex. | | 2022年6月30日 16:58～17:22 ラグナガーデンホテル 羽衣：西 第10会場
1S10e-03
Developmental integration of bottom-up and top-down inputs onto L1 interneurons
*Leena Ali Ibrahim(1,2), Shuhan Huang(2), Marian Fernandez-Otero(2), Mia Sherer(2), Spurti Vemuri(2), Robert Machold, Gabrielle Pouchelon(2), Bernardo Rudy, Gord Fishell(2)
1. King Abdullah University of Science and Technology, 2. Harvard Medical School
Keyword: Layer 1 interneurons, Bottom-up, Top-down, Anterior Cingulate Cortex
Our capacity to perceive and react to a rapidly changing world relies upon the ability of the neocortex to respond accurately and precisely to sensory stimuli. Higher order feedback projections to sensory cortical areas converge upon layer 1 (L1) of the cerebral cortex, the primary site for integration of top-down information via the apical dendrites of pyramidal neurons and L1 GABAergic interneurons. Here, we investigated the contributions of early thalamic inputs onto L1 interneurons for the establishment of top-down inputs in the primary visual cortex. We have found that bottom-up thalamic inputs predominate during early L1 development and preferentially target neurogliaform cells. We also found that these projections are critical for the subsequent strengthening of feedback inputs from the anterior cingulate cortex. Enucleation or selective removal of thalamic afferents blocked this phenomenon. Notably, while early activation of anterior cingulate afferents resulted in a premature strengthening of these top-down inputs to neurogliaform cells, this was also dependent on thalamic inputs. These results demonstrate that the proper establishment of top-down feedback inputs critically depends on bottom-up inputs from the thalamus during early postnatal development | | 2022年6月30日 17:22～17:46 ラグナガーデンホテル 羽衣：西 第10会場
1S10e-04
Adolescent development of top-down circuits for bottom-up novelty detection
Jordan M Ross(1), Georgia Bastos(1), Anna M Rader(1), Connor G Gallimore (1), Antanovia D Ferrell (1), Melanie J Grubisha(2), Robert M Sweet(2), *Jordan P Hamm(1)
1. Georgia State University, Neuroscience Institute, Atlanta, GA, 2. University of Pittsburgh School of Medicine, Departments of Psychiatry and Neurology, Pittsburgh, PA
Keyword: Vision, prefrontal, oscillations, KALRN
Although not diagnostic, difficulties in the processing of sensory information in the context of past and present stimuli are common in a number of neuropsychiatric disorders, serving to ultimately undermine how affected individuals perceive and interpret their world. A classic sensory “oddball” paradigm has been employed to study such sensory-contextual processing functions and deficits in humans and a number of animal models. Herein, a sequence of predictable stimuli (i.e. “redundants”) is occasionally broken by rare or unexpected stimuli (i.e. “deviants”). Basic sensory cortex adapts to redundant stimuli over time, responding with weaker neural activity, while deviant stimuli elicit large responses suggestive of a cortical prediction error—i.e. “deviance detection” responses. The cortical circuit mechanisms of these functions remain largely unknown. Our past work in the visual system has shown that long-range projections from higher brain regions, such as the anterior cingulate area (ACa) in mice, may modulate activity in primary visual cortex (V1) to serve to decrease neural responding under predictable settings but augment responses to contextually unexpected, or “deviant”, stimuli. Specfically, top-down inputs to V1 may be tonically active at approximately 10-Hz during the oddball paradigm and thereby serve to enhance the activity of VIP-positive interneurons in V1 while suppressing SST-positive interneurons. This SST-suppression effectively disinhibits ensembles of pyramidal neurons to release prediction-error-like “deviance detection” responses to unexpected stimuli. Because many neuropsychiatric diseases onset during adolescence, we sought to understand i) how such V1 deviance detection responses develop in adolescence in V1, ii) how long range ACa-V1 synchrony develops, particularly in the 10-Hz range, and iii) whether this top-down modulation is affected in a mouse showing adolescent-period dendritic atrophy (i.e. the Kalrn-PT mutant mouse). Results show that male mice exhibit strong deviance detection responses in V1 in adulthood, but not at P28 or P42. Further, this timeline corresponds to the development ACa-V1 10-Hz synchrony in mice, and such synchrony is severely reduced in Kalrn-PT mice, along with signatures of deviance detection in the LFP. Altogether this suggests that difficulties in sensory-context processing may involve long-range cortical circuits which develop in late adolescence, corresponding to the onset of multiple neuropsychiatric diseases. | | 2022年6月30日 17:46～18:10 ラグナガーデンホテル 羽衣：西 第10会場
1S10e-05
Local and Long-range Balance in Maturing Frontal Cognitive Circuit
*森下 博文(1)
1. マウントサイナイ医科大学
*Hirofumi Morishita Morishita(1)
1. Icahn School of Medicine at Mount Sinai
Keyword: local and long-range balance, adolescence, cognitive control, autism
Cognitive function depends on frontal cortex development; however, the molecular and circuit mechanisms driving this process are poorly understood. Of particular significance among frontal cortical circuits participating in cognitive control are top-down projections from frontal to sensory visual cortical areas. We found that this key top-down circuit receives heightened local excitatory inputs during adolescence compared to adulthood, while long-range inputs are already established prior to adolescence. These developmental changes lead to a shift in the balance of local and long-range input on top-down neurons between adolescence and adulthood. We demonstrated that this shift in local and long-range balance was mediated by the post-adolescent suppression nicotinic tone, an essential developmental milestone to establish proper attentional behavior in adulthood. Of note, this key maturational process was disrupted in a mouse model of fragile X syndrome but was rescued by a suppression of nicotinic tone in top-down projections. Nicotinic signaling may serve as a target to rebalance local and long-range balance and treat cognitive deficits in neurodevelopmental disorders. | | | |
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