The thalamic reticular nucleus (TRN) is a unique brain structure at the interface between the thalamus and the cortex. Because the TRN receives bottom-up sensory input and top-down cortical input, it could serve as an integration hub for sensory and cognitive signals. Functional evidence supports broad roles for the TRN in arousal, attention, and sensory selection. How specific circuits connecting the TRN with sensory thalamic structures implement these functions is not known. The structural organization and function of the TRN is particularly interesting in the context of highly organized sensory systems, such as the primate visual system, where neurons in the retina and dorsal lateral geniculate nucleus of the thalamus (dLGN) are morphologically and physiologically distinct and also specialized for processing particular features of the visual environment. To gain insight into the functional relationship between the visual sector of the TRN and the dLGN, we reconstructed a large number of TRN neurons that were retrogradely labeled following injections of rabies virus expressing enhanced green fluorescent protein (EGFP) into the dLGN. An independent cluster analysis, based on 10 morphological metrics measured for each reconstructed neuron, revealed three clusters of TRN neurons that differed in cell body shape and size, dendritic arborization patterns, and medial-lateral position within the TRN. TRN dendritic and axonal morphologies are inconsistent with visual stream-specific projections to the dLGN. Instead, TRN neuronal organization could facilitate transmission of global arousal and/or cognitive signals to the dLGN with retinotopic precision that preserves specialized processing of foveal versus peripheral visual information.

The corticogeniculate (CG) pathway links the visual cortex with the lateral geniculate nucleus (LGN) of the thalamus and is the first feedback connection in the mammalian visual system. Whether functional connections between CG neurons and LGN relay neurons obey or ignore the separation of feedforward visual signals into parallel processing streams is not known. Accordingly, there is some debate about whether CG neurons are morphologically heterogeneous or homogenous. Here we characterized the morphology of CG neurons in the ferret, a visual carnivore with distinct feedforward parallel processing streams, and compared the morphology of ferret CG neurons with CG neuronal morphology previously described in macaque monkeys [Briggs et al. (2016) Neuron, 90, 388]. We used a G-deleted rabies virus as a retrograde tracer to label CG neurons in adult ferrets. We then reconstructed complete dendritic morphologies for a large sample of virus-labeled CG neurons. Quantification of CG morphology revealed three distinct CG neuronal subtypes with striking similarities to the CG neuronal subtypes observed in macaques. These findings suggest that CG neurons may be morphologically diverse in a variety of highly visual mammals in which feedforward visual pathways are organized into parallel processing streams. Accordingly, these results provide support for the notion that CG feedback is functionally parallel stream-specific in ferrets and macaques.

This protocol outlines large-scale reconstructions of neurons combined with the use of independent and unbiased clustering analyses to create a comprehensive survey of the morphological characteristics observed among a selective neuronal population. Combination of these techniques constitutes a novel approach for the collection and analysis of neuroanatomical data. Together, these techniques enable large-scale, and therefore more comprehensive, sampling of selective neuronal populations and establish unbiased quantitative methods for describing morphologically unique neuronal classes within a population.The protocol outlines the use of modified rabies virus to selectively label neurons. G-deleted rabies virus acts like a retrograde tracer following stereotaxic injection into a target brain structure of interest and serves as a vehicle for the delivery and expression of EGFP in neurons. Large numbers of neurons are infected using this technique and express GFP throughout their dendrites, producing "Golgi-like" complete fills of individual neurons. Accordingly, the virus-mediated retrograde tracing method improves upon traditional dye-based retrograde tracing techniques by producing complete intracellular fills.Individual well-isolated neurons spanning all regions of the brain area under study are selected for reconstruction in order to obtain a representative sample of neurons. The protocol outlines procedures to reconstruct cell bodies and complete dendritic arborization patterns of labeled neurons spanning multiple tissue sections. Morphological data, including positions of each neuron within the brain structure, are extracted for further analysis. Standard programming functions were utilized to perform independent cluster analyses and cluster evaluations based on morphological metrics. To verify the utility of these analyses, statistical evaluation of a cluster analysis performed on 160 neurons reconstructed in the thalamic reticular nucleus of the thalamus (TRN) of the macaque monkey was made. Both the original cluster analysis and the statistical evaluations performed here indicate that TRN neurons are separated into three subpopulations, each with unique morphological characteristics.

Background: Psychedelics have resurged in neuroscience and psychiatry with promising success in psychedelic-assisted therapy for the treatment of anxiety, depression, and addiction. At the cellular level, psychedelics elicit neuroplastic processes 24 hours after administration, priming neural circuits for change. The acute effects of psychedelics are well characterized with functional imaging and neural oscillations showing an increase in the entropy of spontaneous cortical activity. Hypotheses: We hypothesized that cortical-striatal oscillations recorded in rats would confirm the effects of psychedelics. We also hypothesized that brain stimulation delivered 24 hours after LSD administration would lead to different effects than brain stimulation alone. Methods: We recorded local field potential (LFP) oscillations from rats following lysergic acid diethylamide (LSD) or saline administration and determined if exposure to these treatments altered the effect of a targeted intervention (brain stimulation) 24 hours later. Results: We confirmed acutely decreased low frequency power across the brain when rats are given LSD. We also demonstrated these altered states return to baseline after 24 hours. Brain stimulation applied in this window of heightened neuroplasticity produced distinct shifts in brain state compared to brain stimulation applied 24 hours after saline. Conclusions: Despite the acute effects of LSD disappearing after 24 hours, there are still latent effects that synergize with brain stimulation to create different changes in brain activity compared to brain stimulation alone. Our findings are the first to suggest that psychedelics could have a role clinically in combination with brain stimulation to achieve enhanced effects on brain activity and clinical outcomes.

Nicotine and alcohol use is highly prevalent among patients with serious mental illness, including those with schizophrenia (SCZ), and this co-occurrence can lead to a worsening of medical and psychiatric morbidity. While the mechanistic drivers of co-occurring SCZ, nicotine use and alcohol use are unknown, emerging evidence suggests that the use of drugs during adolescence may increase the probability of developing psychiatric disorders. The current study used the neonatal ventral hippocampal lesion (NVHL) rat model of SCZ, which has previously been shown to have enhanced nicotine behavioral sensitization and, following adolescent alcohol, increased alcohol consumption. Given how commonly alcohol is used by adolescents that develop SCZ, we used the NVHL rat to determine how exposure to adolescent alcohol impacts the development of nicotine behavioral sensitization in adulthood. Male Sprague-Dawley rats underwent the NVHL surgery or a sham (control) surgery and subsequently, half of each group was allowed to drink alcohol during adolescence. Nicotine behavioral sensitization was assessed in adulthood with rats receiving subcutaneous injections of nicotine (0.5 mg/kg) each day for 3 weeks followed by a nicotine challenge session 2 weeks later. We demonstrate that all groups of rats became sensitized to nicotine and there were no NVHL-specific increases in nicotine behavioral sensitization. We also found that NVHL rats appeared to develop sensitization to the nicotine paired context and that adolescent alcohol exposure blocked this context sensitization. The current findings suggest that exposure to alcohol during adolescence can influence behaviors that manifest in the adult NVHL rat (i.e., context sensitization). Interestingly, nicotine behavioral sensitization levels were not altered in the NVHL groups regardless of adolescent alcohol exposure in contrast to prior reports.