| | Models | Description |
| 1. |
Computer models of corticospinal neurons replicate in vitro dynamics (Neymotin et al. 2017)
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"Corticospinal neurons (SPI), thick-tufted pyramidal neurons in motor
cortex layer 5B that project caudally via the medullary pyramids,
display distinct class-specific electrophysiological properties in
vitro: strong sag with hyperpolarization, lack of adaptation, and a
nearly linear frequency-current (FI) relationship. We used our
electrophysiological data to produce a pair of large archives of SPI
neuron computer models in two model classes: 1. Detailed models with
full reconstruction; 2. Simplified models with 6 compartments. We
used a PRAXIS and an evolutionary multiobjective optimization (EMO) in
sequence to determine ion channel conductances.
..." |
| 2. |
Deconstruction of cortical evoked potentials generated by subthalamic DBS (Kumaravelu et al 2018)
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"...
High frequency deep brain stimulation (DBS) of the
subthalamic nucleus (STN) suppresses parkinsonian motor symptoms and
modulates cortical activity.
...
Cortical evoked potentials (cEP) generated by STN DBS reflect
the response of cortex to subcortical stimulation, and the goal was to
determine the neural origin of cEP using a two-step approach.
First,
we recorded cEP over ipsilateral primary motor cortex during different
frequencies of STN DBS in awake healthy and unilateral 6-OHDA lesioned
parkinsonian rats.
Second, we used a biophysically-based model of the
thalamocortical network to deconstruct the neural origin of the
cEP. The in vivo cEP included short (R1), intermediate (R2) and
long-latency (R3) responses. Model-based cortical responses to
simulated STN DBS matched remarkably well the in vivo responses.
R1
was generated by antidromic activation of layer 5 pyramidal neurons,
while recurrent activation of layer 5 pyramidal neurons via excitatory
axon collaterals reproduced R2. R3 was generated by polysynaptic
activation of layer 2/3 pyramidal neurons via the
cortico-thalamic-cortical pathway.
Antidromic activation of the
hyperdirect pathway and subsequent intracortical and
cortico-thalamo-cortical synaptic interactions were sufficient to
generate cEP by STN DBS, and orthodromic activation through basal
ganglia-thalamus-cortex pathways was not required. These results
demonstrate the utility of cEP to determine the neural elements
activated by STN DBS that might modulate cortical activity and
contribute to the suppression of parkinsonian symptoms." |
| 3. |
Distinct integration properties of noisy inputs in active dendritic subunits (Poleg-Polsky 2019)
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The brain operates surprisingly well despite the noisy nature of individual neurons. The central mechanism for noise mitigation in the nervous system is thought to involve averaging over multiple noise-corrupted inputs. Subsequently, there has been considerable interest recently to identify noise structures that can be integrated linearly in a way that preserves reliable signal encoding. By analyzing realistic synaptic integration in biophysically accurate neuronal models, I report a complementary de-noising approach that is mediated by focal dendritic spikes. Dendritic spikes might seem to be unlikely candidates for noise reduction due to their miniscule integration compartments and poor averaging abilities. Nonetheless, the extra thresholding step introduced by dendritic spike generation increases neuronal tolerance for a broad category of noise structures, some of which cannot be resolved well with averaging. This property of active dendrites compensates for compartment size constraints and expands the repertoire of conditions that can be processed by neuronal populations. |
| 4. |
Reducing variability in motor cortex activity by GABA (Hoshino et al. 2019)
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Interaction between sensory and motor cortices is crucial for perceptual decision-making, in which intracortical inhibition might have an important role. We simulated a neural network model consisting of a sensory network (NS) and a motor network (NM) to elucidate the significance of their interaction in perceptual decision-making in association with the level of GABA in extracellular space: extracellular GABA concentration. Extracellular GABA molecules acted on extrasynaptic receptors embedded in membranes of pyramidal cells and suppressed them. A reduction in extracellular GABA concentration either in NS or NM increased the rate of errors in perceptual decision-making, for which an increase in ongoing-spontaneous fluctuations in subthreshold neuronal activity in NM prior to sensory stimulation was responsible. Feedback (NM-to-NS) signaling enhanced selective neuronal responses in NS, which in turn increased stimulus-evoked neuronal activity in NM. We suggest that GABA in extracellular space contributes to reducing variability in motor cortex activity at a resting state
and thereby the motor cortex can respond correctly to a subsequent sensory stimulus. Feedback signaling from the motor cortex improves the selective responsiveness of the sensory cortex, which ensures the fidelity of information transmission to the motor cortex, leading to reliable perceptual decision-making. |
