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Pyramidal neurons in prefrontal cortex receive subtype-specific forms of excitation and inhibition.

ABSTRACT: Layer 5 pyramidal neurons comprise at least two subtypes: thick-tufted, subcortically projecting type A neurons, with prominent h-current, and thin-tufted, callosally projecting type B neurons, which lack prominent h-current. Using optogenetic stimulation, we find that these subtypes receive distinct forms of input that could subserve divergent functions. Repeatedly stimulating callosal inputs evokes progressively smaller excitatory responses in type B but not type A neurons. Callosal inputs also elicit more spikes in type A neurons. Surprisingly, these effects arise via distinct mechanisms. Differences in the dynamics of excitatory responses seem to reflect differences in presynaptic input, whereas differences in spiking depend on postsynaptic mechanisms. We also find that fast-spiking parvalbumin interneurons, but not somatostatin interneurons, preferentially inhibit type A neurons, leading to greater feedforward inhibition in this subtype. These differences may enable type A neurons to detect salient inputs that are focused in space and time, while type B neurons integrate across these dimensions.

SUBMITTER: Lee AT

PROVIDER: S-EPMC3947199 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Pyramidal neurons in prefrontal cortex receive subtype-specific forms of excitation and inhibition.

Lee Anthony T AT Gee Steven M SM Vogt Daniel D Patel Tosha T Rubenstein John L JL Sohal Vikaas S VS

Neuron 20131219 1

Layer 5 pyramidal neurons comprise at least two subtypes: thick-tufted, subcortically projecting type A neurons, with prominent h-current, and thin-tufted, callosally projecting type B neurons, which lack prominent h-current. Using optogenetic stimulation, we find that these subtypes receive distinct forms of input that could subserve divergent functions. Repeatedly stimulating callosal inputs evokes progressively smaller excitatory responses in type B but not type A neurons. Callosal inputs als ...[more]

PMID: 24361076

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Project description:Exposure to unpredictable environmental stress is widely recognized as a major determinant for risk and severity in neuropsychiatric disorders such as major depressive disorder, anxiety, schizophrenia, and PTSD. The ability of ostensibly unrelated disorders to give rise to seemingly similar psychiatric phenotypes highlights a need to identify circuit-level concepts that could unify diverse factors under a common pathophysiology. Although difficult to disentangle a causative effect of stress from other factors on medial prefrontal cortex (PFC) dysfunction, a wealth of data from humans and rodents demonstrates that the PFC is a key target of stress. The present study sought to identify a model of chronic unpredictable stress (CUS) which induces affective behaviors in C57BL6J mice and once established, measure stress-related alterations in intrinsic excitability and synaptic regulation of mPFC layer 5/6 pyramidal neurons. Adult male mice received 2 weeks of 'less intense' stress or 2 or 4 weeks of 'more intense' CUS followed by sucrose preference for assessment of anhedonia, elevated plus maze for assessment of anxiety and forced swim test for assessment of depressive-like behaviors. Our findings indicate that more intense CUS exposure results in increased anhedonia, anxiety, and depressive behaviors, while the less intense stress results in no measured behavioral phenotypes. Once a behavioral model was established, mice were euthanized approximately 21 days post-stress for whole-cell patch clamp recordings from layer 5/6 pyramidal neurons in the prelimbic (PrL) and infralimbic (IL) cortices. No significant differences were initially observed in intrinsic cell excitability in either region. However, post-hoc analysis and subsequent confirmation using transgenic mice expressing tdtomato or eGFP under control of dopamine D1-or D2-type receptor showed that D1-expressing pyramidal neurons (D1-PYR) in the PrL exhibit reduced thresholds to fire an action potential (increased excitability) but impaired firing capacity at more depolarized potentials, whereas D2-expressing pyramidal neurons (D2-PYR) showed an overall reduction in excitability and spike firing frequency. Examination of synaptic transmission showed that D1-and D2-PYR exhibit differences in basal excitatory and inhibitory signaling under naïve conditions. In CUS mice, D1-PYR showed increased frequency of both miniature excitatory and inhibitory postsynaptic currents, whereas D2-PYR only showed a reduction in excitatory currents. These findings demonstrate that D1-and D2-PYR subpopulations differentially undergo stress-induced intrinsic and synaptic plasticity that may have functional implications for stress-related pathology, and that these adaptations may reflect unique differences in basal properties regulating output of these cells.

Dataset Information

Pyramidal neurons in prefrontal cortex receive subtype-specific forms of excitation and inhibition.

Publications

Pyramidal neurons in prefrontal cortex receive subtype-specific forms of excitation and inhibition.

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