Cortical Inactivation by Cooling in Small Animals

Abstract

Reversible inactivation of the cortex by surface cooling is a powerful method for studying the function of a particular area. Implanted cooling cryoloops have been used to study the role of individual cortical areas in auditory processing of awake-behaving cats. Cryoloops have also been used in rodents for reversible inactivation of the cortex, but recently there has been a concern that the cryoloop may also cool non-cortical structures either directly or via the perfusion of blood, cooled as it passed close to the cooling loop. In this study we have confirmed that the loop can inactivate most of the auditory cortex without causing a significant reduction in temperature of the auditory thalamus or other subcortical structures. We placed a cryoloop on the surface of the guinea pig cortex, cooled it to 2°C and measured thermal gradients across the neocortical surface. We found that the temperature dropped to 20–24°C among cells within a radius of about 2.5 mm away from the loop. This temperature drop was sufficient to reduce activity of most cortical cells and led to the inactivation of almost the entire auditory region. When the temperature of thalamus, midbrain, and middle ear were measured directly during cortical cooling, there was a small drop in temperature (about 4°C) but this was not sufficient to directly reduce neural activity. In an effort to visualize the extent of neural inactivation we measured the uptake of thallium ions following an intravenous injection. This confirmed that there was a large reduction of activity across much of the ipsilateral cortex and only a small reduction in subcortical structures.

Effect of Auditory Cortex Deactivation on Stimulus-Specific Adaptation in the Medial Geniculate Body

“…1). The normal AC surface temperature was regained in a few minutes, though cortical and MGB responses took longer to return to normal (Nakamoto et al, 2008;Coomber et al, 2011). After 30 min, the responses of the neurons returned to normal, since cooling disrupts neither the structural nor functional integrity of the cooled area Yang et al, 2006) (Fig.…”

“…It has been extensively used to study functional interactions between cortical areas in cat (Ghosh et al, 1994;Lomber, 1999;Lomber et al, 1999;Lomber and Malhotra, 2008;Carrasco and Lomber, 2009a,b) and the corticofugal modulation of subcortical nuclei in various sensory systems. In smaller animals, such as the guinea pig, cooling has been demonstrated to reliably deactivate the AC without causing a reduction in temperature sufficient to directly reduce neural activity in the MGB and other subcortical nuclei (Coomber et al, 2011). It is assumed that ipsilateral AC cooling deactivated all the descending inputs to the MGB, since corticofugal fibers terminating in this nucleus are entirely ipsilateral (Bajo et al, 1995(Bajo et al, , 2010Ojima and Rouiller, 2011).…”

“…1). This technique enables the reversible deactivation of discrete regions of the brain (Lomber, 1999;Lomber and Malhotra, 2008;Carrasco and Lomber, 2009a,b;Coomber et al, 2011). It has been extensively used to study functional interactions between cortical areas in cat (Ghosh et al, 1994;Lomber, 1999;Lomber et al, 1999;Lomber and Malhotra, 2008;Carrasco and Lomber, 2009a,b) and the corticofugal modulation of subcortical nuclei in various sensory systems.…”

“…1a). These measurements were made with an Omega 5SC-TT-KI thermo-probe, composed of two wires (76 m diameter and plastic insulated) welded together to form a bead of 225 m diameter, as described by Coomber et al (2011). The responses of the MGB neurons (FRAs and SSA) were recorded during ϳ15 min of AC deactivation, after which the cryoloop pump was turned off (Fig.…”

“…There was a small drop in the MGB temperature (ϳ5°C), but it never fell to 26°C (Fig. 1), a temperature that is above the 24 -20°C necessary to reduce neural activity Coomber et al, 2011). To elicit SSA in the MGB neurons, we used trains of two different puretone stimuli in an oddball paradigm ( f 1 and f 2 ; 400 stimulus presentations in two blocks) (Figs.…”