Single-photon optogenetics enables precise, cell-type-specific modulation of neuronal circuits, making it a crucial tool in neuroscience. Its miniaturization in the form of fully implantable wide-field stimulator arrays enables long-term interrogation of cortical circuits and bears promise for brain-machine interfaces for sensory and motor function restoration. However, achieving selective activation of functional cortical representations poses a challenge, as studies show that targeted optogenetic stimulation results in activity spread beyond one functional domain. While recurrent network mechanisms contribute to activity spread, here we demonstrate with detailed simulations of isolated pyramidal neurons from cats of unknown sex that already neuron morphology causes a complex spread of optogenetic activity at the scale of one cortical column. Since the shape of a neuron impacts its optogenetic response, we find that a single stimulator at the cortical surface recruits a complex spatial distribution of neurons that can be inhomogeneous and vary with stimulation intensity and neuronal morphology across layers. We explore strategies to enhance stimulation precision, finding that optimizing stimulator optics may offer more significant improvements than the preferentially somatic expression of the opsin through genetic targeting. Our results indicate that, with the right optical setup, single-photon optogenetics can precisely activate isolated neurons at the scale of functional cortical domains spanning several hundred micrometers.
- MeSH
- Cats MeSH
- Models, Neurological MeSH
- Cerebral Cortex physiology cytology MeSH
- Neurons physiology MeSH
- Optogenetics * methods MeSH
- Pyramidal Cells physiology MeSH
- Photic Stimulation methods MeSH
- Animals MeSH
- Check Tag
- Cats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Extrapyramidal Tracts anatomy & histology physiology MeSH
- Humans MeSH
- Motor Cortex * anatomy & histology physiology MeSH
- Primary Visual Cortex anatomy & histology physiology MeSH
- Pyramidal Cells physiology MeSH
- Pyramidal Tracts anatomy & histology physiology MeSH
- Sensorimotor Cortex anatomy & histology physiology MeSH
- Auditory Cortex anatomy & histology physiology MeSH
- Somatosensory Cortex anatomy & histology physiology MeSH
- Vestibular System anatomy & histology physiology innervation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Electroencephalography MeSH
- CA3 Region, Hippocampal anatomy & histology physiology MeSH
- Rats MeSH
- Brain Waves physiology MeSH
- Memory * physiology classification MeSH
- Pyramidal Cells physiology MeSH
- Mental Recall physiology MeSH
- Check Tag
- Rats MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Electroencephalography MeSH
- Hippocampus physiology physiopathology drug effects MeSH
- Models, Animal MeSH
- Nerve Net MeSH
- Memory * physiology drug effects MeSH
- Rats, Long-Evans MeSH
- Pyramidal Cells physiology pathology MeSH
- Receptors, N-Methyl-D-Aspartate antagonists & inhibitors administration & dosage MeSH
- Mental Recall physiology drug effects MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Experimental and computational studies emphasize the role of the millisecond precision of neuronal spike times as an important coding mechanism for transmitting and representing information in the central nervous system. We investigate the spike time precision of a multicompartmental pyramidal neuron model of the CA3 region of the hippocampus under the influence of various sources of neuronal noise. We describe differences in the contribution to noise originating from voltage-gated ion channels, synaptic vesicle release, and vesicle quantal size. We analyze the effect of interspike intervals and the voltage course preceding the firing of spikes on the spike-timing jitter. The main finding of this study is the ranking of different noise sources according to their contribution to spike time precision. The most influential is synaptic vesicle release noise, causing the spike jitter to vary from 1 ms to 7 ms of a mean value 2.5 ms. Of second importance was the noise incurred by vesicle quantal size variation causing the spike time jitter to vary from 0.03 ms to 0.6 ms. Least influential was the voltage-gated channel noise generating spike jitter from 0.02 ms to 0.15 ms.
- MeSH
- Action Potentials physiology MeSH
- Time Factors MeSH
- Hippocampus physiology MeSH
- Noise MeSH
- Rats MeSH
- Humans MeSH
- Models, Neurological MeSH
- Synaptic Transmission MeSH
- Neurons metabolism physiology MeSH
- Computer Simulation MeSH
- Pyramidal Cells physiology MeSH
- Software MeSH
- Models, Theoretical MeSH
- Calcium Channels metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
N-methyl-d-aspartate (NMDA) receptors (NMDARs) are highly expressed in the CNS and mediate the slow component of excitatory transmission. The present study was aimed at characterizing the temperature dependence of the kinetic properties of native NMDARs, with special emphasis on the deactivation of synaptic NMDARs. We used patch-clamp recordings to study synaptic NMDARs at layer II/III pyramidal neurons of the rat cortex, recombinant GluN1/GluN2B receptors expressed in human embryonic kidney (HEK293) cells, and NMDARs in cultured hippocampal neurons. We found that time constants characterizing the deactivation of NMDAR-mediated excitatory postsynaptic currents (EPSCs) were similar to those of the deactivation of responses to a brief application of glutamate recorded under conditions of low NMDAR desensitization (whole-cell recording from cultured hippocampal neurons). In contrast, the deactivation of NMDAR-mediated responses exhibiting a high degree of desensitization (outside-out recording) was substantially faster than that of synaptic NMDA receptors. The time constants characterizing the deactivation of synaptic NMDARs and native NMDARs activated by exogenous glutamate application were only weakly temperature sensitive (Q(10)=1.7-2.2), in contrast to those of recombinant GluN1/GluN2B receptors, which are highly temperature sensitive (Q(10)=2.7-3.7). Ifenprodil reduced the amplitude of NMDAR-mediated EPSCs by approximately 50% but had no effect on the time course of deactivation. Analysis of GluN1/GluN2B responses indicated that the double exponential time course of deactivation reflects mainly agonist dissociation and receptor desensitization. We conclude that the temperature dependences of native and recombinant NMDAR are different; in addition, we contribute to a better understanding of the molecular mechanism that controls the time course of NMDAR-mediated EPSCs. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
- MeSH
- Excitatory Amino Acid Antagonists pharmacology MeSH
- Cell Line MeSH
- Excitatory Postsynaptic Potentials physiology drug effects MeSH
- Hippocampus physiology drug effects MeSH
- Kinetics MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Glutamic Acid metabolism MeSH
- Humans MeSH
- Cerebral Cortex physiology drug effects MeSH
- Synaptic Transmission physiology drug effects MeSH
- Piperidines pharmacology MeSH
- Rats, Wistar MeSH
- Pyramidal Cells physiology drug effects MeSH
- Receptors, N-Methyl-D-Aspartate metabolism MeSH
- Synapses physiology drug effects MeSH
- In Vitro Techniques MeSH
- Temperature MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
It has been suggested that in mammals, trigeminal lamina I neurons play a role in the processing and transmission of sensory information from the orofacial region. We investigated the physiological and morphological properties of trigeminal subnucleus caudalis (Sp5C) lamina I neurons in slices prepared from the medulla oblongata of 13- to 15-day-old postnatal rats using patch-clamp recordings and subsequent biocytin-streptavidin-Alexa labeling. Twenty-five neurons were recorded and immunohistochemically stained. The Sp5C lamina I consisted of several types of neurons which, on the basis of their responses to somatic current injection, can be classified into four groups: tonic neurons, which fired throughout the depolarizing pulse; phasic neurons, which expressed an initial burst of action potentials; delayed onset neurons, which showed a significant delay of the first action potential; and single spike neurons, characterized by only one to five action potentials at the very beginning of the depolarizing pulse even at high levels of stimulation intensity. Electrical stimulation of the spinal trigeminal tract evoked AMPA receptor-mediated excitatory postsynaptic currents (EPSC) exhibiting a strong polysynaptic component. AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSC) were characterized by a 10-90% rise time of 0.50+/-0.06 ms and a decay time constant of 2.5+/-0.5 ms. The kinetic properties of NMDA receptor-mediated EPSCs were measured at +40 mV. The 10-90% rise time was 8+/-2 ms and the deactivation time constants were 94+/-31 and 339+/-72 ms, respectively. Intracellular staining and morphological analysis revealed three groups of neurons: fusiform, pyramidal, and multipolar. Statistical analysis indicated that the electrophysiological properties and morphological characteristics are correlated. Tonic and phasic neurons were fusiform or pyramidal and delayed onset and single spike neurons were multipolar. Our results show that both the physiological and morphological properties of Sp5C lamina I neurons exhibit significant differences, indicating their specific integration in the processing and transmission of sensory information from the orofacial region.
- MeSH
- Algorithms MeSH
- Receptors, AMPA physiology MeSH
- Electrophysiology MeSH
- Excitatory Postsynaptic Potentials physiology MeSH
- Financing, Organized MeSH
- Immunohistochemistry MeSH
- Data Interpretation, Statistical MeSH
- Rats MeSH
- Membrane Potentials physiology MeSH
- Patch-Clamp Techniques MeSH
- Trigeminal Nuclei anatomy & histology physiology MeSH
- Cell Polarity physiology MeSH
- Rats, Wistar MeSH
- Pyramidal Cells physiology MeSH
- Receptors, N-Methyl-D-Aspartate physiology MeSH
- Synapses physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
