Neocortical microcircuits: Role of excitatory feedback circuits within a barrel-related cortical column
Final Report Abstract
During the funding period 2013-2016 we have further investigated the structural and functional synaptic connectivity of excitatory and inhibitory neurons in the barrel cortex. In a first set of experiments we focussed on synaptic connections between layer 6 pyramidal cells and investigated the synaptic release properties of these connections. Because layer 6 contains are highly diverse number of excitatory neurons we had to characterise these neurons in the first place and then went on to investigate their synaptic release properties. Connections between all types of L6 spiny neurons exhibit a rather low release probability despite being strongly interconnected which is in contrast to most other excitatory connections in the barrel cortex. To identify different neuron types in layer 6 we investigated whether neurons in this layer can be distinguished based on the expression of cellular molecular markers. Because the transcription factor FoxP2 is exclusively expressed in layer 6 we tested whether it labelled specific L6 spiny neuron cell types. We found that in Layer 6A it labels specifically corticothalamic L6A pyramidal cells but not those with a corticocortical axonal projection; in layer 6B all pyramidal cell but no other L6B spiny neuron type showed FoxP2 labelling. The pattern of FoxP2 expression may in the future help to delineate specific neuronal microcircuits in layer 6 of the barrel cortex. A particular feature of layer 6B is its high diversity of excitatory, spine-bearing neurons the origin of which is still a matter of debate. In a collaborative study we investigated whether a subset of L6B neurons could be persistent subplate neurons. We found that L6B and suplate neurons share common features supporting the idea that layer 6B is a remnant of the subplate. In another subproject we investigated how neuromodulatory transmitters that are released during different behavioural states affect synaptic transmission of excitatory and inhibitory neurons in the barrel cortex. Here we concentrated on the effects of adenosine and noradrenaline and found that they had cell-specific effects on different neuron types thereby shifting the synaptic signalling pathways. Furthermore, they change the excitation-inhibition balance which suggests that the functional synaptic connectivity is far more complex than previously thought. While the excitatory connectivity in the barrel cortex is relatively well known data on inhibitory synaptic connections is just beginning to emerge. In this subproject of the proposal we investigated non-fast spiking (nFS) interneurons and their synaptic connections. We found three different types with either local, or translaminar or transcolumnar axonal projections. Almost all nFS interneurons in layer 4 established synaptic connections with excitatory neurons and other interneurons which showed a low release probability and synaptic facilitation following prolonged activity. We also identified a novel type of excitatory and inhibitory synaptic connection in layer 4 of the barrel cortex. In contrast to the widely accepted that their is little cross-talk between cortical barrels we found that both excitatory and inhibitory neurons form synaptic contacts with neurons in adjacent barrels. These findings may explain the rather large receptive fields found in in vivo studies and provide a cellular correlate for lateral inhibition.
Publications
- (2013) Barrel cortex function. Prog Neurobiol 103:3-27
Feldmeyer D, Brecht M, Helmchen F, Petersen CC, Poulet JF, Staiger JF, Luhmann HJ, Schwarz C
(See online at https://doi.org/10.1016/j.pneurobio.2012.11.002) - (2013) Morphology and physiology of excitatory neurons in layer 6b of the somatosensory rat barrel cortex. Cereb Cortex 23:2803-2817
Marx M, Feldmeyer D
(See online at https://doi.org/10.1093/cercor/bhs254) - (2015) A barrel-related interneuron in layer 4 of rat somatosensory cortex with a high intrabarrel connectivity. Cereb Cortex 25:713-725
Koelbl C, Helmstaedter M, Lübke J, Feldmeyer D
(See online at https://doi.org/10.1093/cercor/bht263) - (2015) Contribution of intracolumnar layer 2/3-to-layer 2/3 excitatory connections in shaping the response to whisker deflection in rat barrel cortex. Cereb Cortex 25:849-858
Sarid L, Feldmeyer D, Gidon A, Sakmann B, Segev I
(See online at https://doi.org/10.1093/cercor/bht268) - (2015) Neocortical layer 6B as a remnant of the subplate - a morphological comparison. Cereb Cortex
Marx M, Qi G, Hanganu-Opatz IL, Kilb W, Luhmann HJ, Feldmeyer D
(See online at https://doi.org/10.1093/cercor/bhv279) - (2015) S1 Microcircuits. Scholarpedia 10:7458
Feldmeyer D
(See online at https://doi.org/10.4249/scholarpedia.7458) - (2015) Structural determinants underlying the high efficacy of synaptic transmission and plasticity at synaptic boutons in layer 4 of the adult rat 'barrel cortex'. Brain Struct Funct 220:3185-3209
Rollenhagen A, Klook K, Sätzler K, Qi G, Anstötz M, Feldmeyer D, Lübke JH
(See online at https://doi.org/10.1007/s00429-014-0850-5) - (2015) Synaptic microcircuits in the barrel cortex. In: Sensorimotor integration in the whisker system (Krieger P, Groh A, eds), pp 59-108. New York: Springer
Radnikow G, Qi G, Feldmeyer D
(See online at https://doi.org/10.1007/978-1-4939-2975-7_4) - (2016) Adenosine differentially modulates synaptic transmission of excitatory and inhibitory microcircuits in layer 4 of rat barrel cortex. Cereb Cortex
Qi G, van Aerde KI, Abel T, Feldmeyer D
(See online at https://doi.org/10.1093/cercor/bhw243) - (2016) Dendritic target region-specific formation of synapses between excitatory layer 4 neurons and layer 6 pyramidal cells. Cereb Cortex 26:1569-1579
Qi G, Feldmeyer D
(See online at https://doi.org/10.1093/cercor/bhu334)
