• Balance Between Inhibition and Excitation in Rat Prefrontal Cortex: Modulation by Dopamine, As a Study of Age and Cortical Layer

      Toreson, Kathy Lynn; O'Donnell, Patricio (2010)
      Prefrontal cortical (PFC) pyramidal neurons and fast spiking interneurons receive dopaminergic (DA) and non-DAergic inputs from the ventral tegmental area (VTA). In vivo juxtacellular recordings of neurons in the medial PFC were performed to assess the effect of mesocortical activation. Recorded cells were identified as pyramidal neurons or fast spiking interneurons based on electrophysiological characteristics combined with Neurobiotin staining and parvalbumin immunohistochemistry. Chemical activation of the mesocortical pathway (intra-VTA NMDA microinjection) resulted in an increase in firing in fast spiking interneurons and a decrease in firing in pyramidal neurons. These responses had a similar temporal course, suggesting that mesocortical activation of fast spiking interneurons may contribute to the silencing of pyramidal neurons under these conditions. The PFC is organized into layers, which have distinct compositions of cell types, receptor expression, and afferent and efferent projections. Importantly, the density and distribution of dopamine receptors and mesocortical inputs across cortical layers continue to change as the brain matures and does not reach their final arrangements until after puberty. The functional significance of these variations in cortical layer composition and juvenile and versus developmentally mature PFC remain to be determined. To investigate the effect of mesocortical projection activation on pyramidal neurons of the medial prefrontal cortex as a function of cortical layer and late postnatal development, we performed in vivo juxtacellular recordings in juvenile (P28-35) and young adult (>P60) chloral hydrate anesthetized rats. Activation of the VTA by an electrical stimulation that mimics dopamine cell burst firing (5 pulse 20 Hz train) produced either a simple excitatory or inhibitory response, or a complex multiphasic response, in pyramidal neurons. The most common initial (train) response to electrical stimulation of the VTA in both the juvenile and the young adult groups was inhibition. In both age groups, the delayed (post stimulation train) response was approximately equal in the proportions of cells exhibiting excitation or inhibition. When taking into account cortical layer, there was no difference in the proportion of cells exhibiting excitation or inhibition in either age group. These data demonstrate that although there are variations in the composition of cortical layers, as well as anatomical differences between juvenile and adult PFC, these disparities do not result in major differences in the way pyramidal neurons respond to mesocortical activation.
    • Mapping of Cannabinoid Type 1 Receptor Inputs into Dopamine Neurons of the Ventral Tegmental Area

      Kashtelyan, Vadim; Cheer, Joseph F.; Morales, Marisela (2015)
      The mesolimbic dopamine (DA) pathway is critically involved in reward-seeking and appetitive behaviors. It originates in the ventral tegmental area (VTA) and provides DA innervation to terminal regions. Impaired DA transmission is a hallmark of schizophrenia, depression and drug abuse. The activity of DAergic cells is potently modulated by the endocannabinoid system (ECS). The ECS influences neuronal activity through presynaptic inhibition of neurotransmitter release. The cannabinoid type 1 receptor (CB1R) is the main receptor involved in this signaling pathway. Here, we identify inputs to VTA DA neurons that express CB1R mRNA. Using a series of viral vectors, we first identified monosynaptic inputs to DA neurons in the VTA. We then performed a combination of radioactive in situ hybridization and immunohistochemistry to label monosynaptic inputs expressing CB1R mRNA. Our results identify a population of VTA DA afferent neurons arising from the dorsal raphe nucleus that signal through the ECS.