The choroid is richly innervated by parasympathetic, sympathetic and trigeminal sensory nerve fibers that regulate choroidal blood flow in birds and mammals, and presumably other vertebrate classes as well. The parasympathetic innervation has been shown to vasodilate and increase choroidal blood flow, the sympathetic input has been shown to vasoconstrict and decrease choroidal blood flow, and the sensory input has been shown to both convey pain and thermal information centrally and act locally to vasodilate and increase choroidal blood flow. As the choroid lies behind the retina and cannot respond readily to retinal metabolic signals, its innervation is important for adjustments in flow required by either retinal activity, by fluctuations in the systemic blood pressure driving choroidal perfusion, and possibly by retinal temperature. The former two appear to be mediated by the sympathetic and parasympathetic nervous systems, via central circuits responsive to retinal activity and systemic blood pressure, but adjustments for ocular perfusion pressure also appear to be influenced by local autoregulatory myogenic mechanisms. Adaptive choroidal responses to temperature may be mediated by trigeminal sensory fibers. Impairments in the neural control of choroidal blood flow occur with aging, and various ocular or systemic diseases such as glaucoma, age-related macular degeneration (AMD), hypertension, and diabetes, and may contribute to retinal pathology and dysfunction in these conditions, or in the case of AMD be a precondition. The present manuscript reviews findings in birds and mammals that contribute to the above-summarized understanding of the roles of the autonomic and sensory innervation of the choroid in controlling choroidal blood flow, and in the importance of such regulation for maintaining retinal health.

The mammalian striatum receives its main excitatory input from the two types of cortical pyramidal neurons of layer 5 of the cerebral cortex – those with only intratelencephalic connections (IT-type) and those sending their main axon to the brainstem via the pyramidal tract (PT-type). These two neurons types are present in layer 5 of all cortical regions, and thus they appear to project together to all parts of striatum. These two neuron types, however, differ genetically, morphologically, and functionally, with IT-type neurons conveying sensory and motor planning information to striatum and PT-type neurons conveying an efference copy of motor commands (for motor cortex at least). Anatomical and physiological data for rats, and more recent data for primates, indicate that these two cortical neuron types also differ in their targeting of the two main types of striatal projection neurons, with the IT-type input preferentially innervating direct pathway neurons and the PT-type input preferentially innervating indirect pathway striatal neurons. These findings have implications for understanding how the direct and indirect pathways carry out their respective roles in movement facilitation and movement suppression, and they have implications for understanding the role of corticostriatal synaptic plasticity in adaptive motor control by the basal ganglia.

Although dystonia represents a major source of motor disability in Huntington's disease (HD), its pathophysiology remains unknown. Because recent animal studies indicate that loss of parvalbuminergic (PARV+) striatal interneurons can cause dystonia, we investigated if loss of PARV+ striatal interneurons occurs during human HD progression, and thus might contribute to dystonia in HD. We used immunolabeling to detect PARV+ interneurons in fixed sections, and corrected for disease‐related striatal atrophy by expressing PARV+ interneuron counts in ratio to interneurons co‐containing somatostatin and neuropeptide Y (whose numbers are unaffected in HD). At all symptomatic HD grades, PARV+ interneurons were reduced to less than 26% of normal abundance in rostral caudate. In putamen rostral to the level of globus pallidus, loss of PARV+ interneurons was more gradual, not dropping off to less than 20% of control until grade 2. Loss of PARV+ interneurons was even more gradual in motor putamen at globus pallidus levels, with no loss at grade 1, and steady grade‐wise decline thereafter. A large decrease in striatal PARV+ interneurons, thus, occurs in HD with advancing disease grade, with regional variation in the loss per grade. Given the findings of animal studies and the grade‐wise loss of PARV+ striatal interneurons in motor striatum in parallel with the grade‐wise appearance and worsening of dystonia, our results raise the possibility that loss of PARV+ striatal interneurons is a contributor to dystonia in HD.

Summary: Huntington's disease (HD) is a hereditary progressive neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the protein huntingtin, resulting in a pathogenic expansion of the polyglutamine tract in the N‐terminus of this protein. The HD pathology resulting from the mutation is most prominent in the striatal part of the basal ganglia, and progressive differential dysfunction and loss of striatal projection neurons and interneurons account for the progression of motor deficits seen in this disease. The present review summarizes current understanding regarding the progression in striatal neuron dysfunction and loss, based on studies both in human HD victims and in genetic mouse models of HD. We review evidence on early loss of inputs to striatum from cortex and thalamus, which may be the basis of the mild premanifest bradykinesia in HD, as well as on the subsequent loss of indirect pathway striatal projection neurons and their outputs to the external pallidal segment, which appears to be the basis of the chorea seen in early symptomatic HD. Later loss of direct pathway striatal projection neurons and their output to the internal pallidal segment account for the severe akinesia seen late in HD. Loss of parvalbuminergic striatal interneurons may contribute to the late dystonia and rigidity.

Emotional disorders are a common outcome from mild traumatic brain injury (TBI) in humans, but their pathophysiological basis is poorly understood. We have developed a mouse model of closed-head blast injury using an air pressure wave delivered to a small area on one side of the cranium, which we have used to create mild TBI. We found that 20-psi blasts in 3-month old C57BL/6 male mice yielded no obvious behavioral or histological evidence of brain injury, while 25-40 psi blasts produced transient anxiety in an open field arena but little histological evidence of brain damage. By contrast, 50-60 psi blasts resulted in anxiety-like behavior in an open field arena that became more evident with time after blast. In additional behavioral tests conducted 2-8 weeks after blast, 50-60 psi mice also demonstrated increased acoustic startle, perseverance of learned fear, and enhanced contextual fear, as well as depression-like behavior and diminished prepulse inhibition. We found no evident cerebral pathology, however, and only scattered axonal degeneration in brain sections from 50-60 psi mice 3-8 weeks after blast. Thus, the TBI caused by single 50-60 psi blasts in mice exhibits the minimal neuronal loss coupled to “diffuse” axonal injury characteristic of human mild TBI. A reduction in the abundance of a subpopulation of excitatory projection neurons in basolateral amygdala enriched in Thy1 was, however, observed. The reported link of this neuronal population to fear suppression suggests their damage by mild TBI may contribute to the heightened anxiety and fearfulness observed after blast in our mice. Our overpressure air blast model of concussion in mice will enable further studies of the mechanisms underlying the diverse emotional deficits seen after mild TBI.