The impact of hemodynamic stress on sensory signal processing in the rodent lateral geniculate nucleus

Abstract

Hemodynamic stress via hypotensive challenge has been shown previously to cause a corticotropin-releasing factor (CRF)-mediated increase in tonic locus coeruleus (LC) activity and consequent release of norepinephrine (NE) in noradrenergic terminal fields. Although alterations in LC-NE can modulate the responsiveness of signal processing neurons along sensory pathways, little is understood regarding how continuous CRF-mediated activation of LC-NE output due to physiologically relevant stressor affects downstream target cell physiology. The goal of the present study was to investigate the effects of a physiological stressor [hemodynamic stress via sodium nitroprusside (SNP) i.v.] on stimulus evoked responses of sensory processing neurons that receive LC inputs. In rat, the dorsal lateral geniculate nucleus (dLGN) of the thalamus is the primary relay for visual information and is a major target of the LC-NE system. We used extracellular recording techniques in the anesthetized rat monitor single dLGN neuron activity during repeated presentation of light stimuli before and during hemodynamic stress. A significant decrease in magnitude occurred, as well as an increase in latency of dLGN stimulus-evoked responses were observed during hemodynamic stress. In another group of animals the CRF antagonist DpheCRF12–41 was infused onto the ipsilateral LC prior to SNP administration. This infusion blocked the hypotension-induced changes in dLGN stimulus-evoked discharge. These results show that CRF-mediated increases in LC-NE due to hemodynamic stress disrupts the transmission of information along thalamic-sensory pathways by: (1) initially reducing signal transmission during onset of the stressor and (2) decreasing the speed of stimulus evoked sensory transmission.

Effects of intracerebroventricular corticotropin releasing factor on sensory-evoked responses in the rat visual thalamus

“…In contrast to more slowly acting ICV CRF, hemodynamic stress and direct infusion of CRF onto the LC have been shown to intensely activate LC neurons and cause rapid increases in terminal field concentrations of NE (Curtis et al, 1997; Page and Abercrombie, 1999; Palamarchouk et al, 2000; Zhang et al, 1998; Kawahara et al, 1999; Lavicky and Dunn, 1993; Swiergiel et al, 1998). We propose the mode of LC activation and time course of NE release in downstream targets, specifically the more gradual activation of LC and release of NE after ICV CRF administration likely account for the differences in the modulatory effects observed here and in our previous study using hemodynamic stress (Zitnik et al, 2013). Anesthesia affects the dynamics of sensory signal processing, a factor that could also account for differences between the results of the present study and prior reports (Devilbiss et al, 2012).…”

“…As such the LC-thalamic interactions observed may have been representative of the right limb of the inverted-U curve, suppressing stimulus-evoked neuronal responses rather than elevating them. We recently reported suppression of visually evoked neuronal responses in rat thalamus during hemodynamic stress and subsequent CRF-mediated activation of the LC (Zitnik et al, 2013). In contrast to more slowly acting ICV CRF, hemodynamic stress and direct infusion of CRF onto the LC have been shown to intensely activate LC neurons and cause rapid increases in terminal field concentrations of NE (Curtis et al, 1997; Page and Abercrombie, 1999; Palamarchouk et al, 2000; Zhang et al, 1998; Kawahara et al, 1999; Lavicky and Dunn, 1993; Swiergiel et al, 1998).…”

“…Recording methods and offline sorting of single unit waveforms, using Plexon © Offline Sorter were identical to Zitnik et al 2013. Computer-generated cumulative rasters and PSTHs were constructed from the data recorded from each cell in order to characterize and quantify unit responses to light stimuli before and after ICV CRF infusions.…”

“…Recent findings suggest that CRF-mediated activation of the LC-NE system is a contributing factor. Acute exposure to a physiological stressor alters single neuron responsiveness to sensory stimuli by a LC-CRF-dependent mechanism (Zitnik et al, 2013). Additionally, local application of CRF onto the LC was shown to modulate thalamic and cortical sensory evoked responses (Devilbiss et al, 2012).…”

Chronic stress induces significant gene expression changes in the prefrontal cortex alongside alterations in adult hippocampal neurogenesis

“…Both rat and mouse studies find activation of immune response-related gene networks and signalling pathways often centred on nuclear factor kappa B ( Malki et al , 2013 , 2015 ; Gray et al , 2014 ). A number of other studies investigating the effect of chronic mild or restraint stress on hippocampal gene expression in rats and mice identified signalling pathways involved in cell fate, such as cell apoptosis ( Bergström et al , 2007 ), proliferation and cell cycle control ( Liu et al , 2010 ), axonal guidance and cell migration ( Jungke et al , 2011 ; Datson et al , 2012 ; Zitnik et al , 2013 ).…”