Differential Sensitization of Amygdala Neurons to Afferent Inputs in a Model of Arthritic Pain

Pain is associated with negative affect such as anxiety and depression. The amygdala plays a key role in emotionality and has been shown to undergo neuroplastic changes in models of affective disorders. Many neurons in the central nucleus of the amygdala (CeA) are driven by nociceptive inputs, but the role of the amygdala in persistent pain states is not known. This study is the first to address nociceptive processing by CeA neurons in a model of prolonged pain. Extracellular single-unit recordings were made from 41 CeA neurons in anesthetized rats. Each neuron's responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Background activity, receptive field size, and threshold were mapped, and stimulus-response functions were constructed. These parameters were measured repeatedly before and after induction of arthritis in one knee by intraarticular injections of kaolin and carrageenan. Multireceptive (MR) amygdala neurons ( n = 20) with excitatory input from the knee joint responded more strongly to noxious than to innocuous mechanical stimuli of deep tissue ( n = 20) and skin ( n = 11). After induction of arthritis, 18 of 20 MR neurons developed enhanced responses to mechanical stimuli and expansion of receptive field size. These changes occurred with a biphasic time course (early peak: 1–1.5 h; persistent plateau phase: after 3–4 h). Responses to thermal stimuli did not change (7 of 7 neurons), but background activity (16 of 18 neurons) and electrically evoked orthodromic activity (11 of 12 neurons) increased in the arthritic state. Nociceptive-specific (NS) neurons ( n = 13) showed no changes of their responses to mechanical, thermal, and electrical stimulation after induction of arthritis. A third group of neurons did not respond to somesthetic stimuli under control conditions (noSOM neurons; n = 8) but developed prolonged responses to mechanical, but not thermal, stimuli in arthritis (5 of 8 neurons). These data suggest that prolonged pain is accompanied by enhanced responsiveness of a subset of CeA neurons. Their sensitization to mechanical, but not thermal, stimuli argues against a nonspecific state of hyperexcitability. MR neurons could serve to integrate and evaluate information in the context of prolonged pain. Recruitment of noSOM neurons increases the gain of amygdala processing. NS neurons preserve the distinction between nociceptive and nonnociceptive inputs.

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Acute Effect of an Incision on Mechanosensitive Afferents in the Plantar Rat Hindpaw

Journal of Neurophysiology ◽

10.1152/jn.00207.2001 ◽

2002 ◽

Vol 87 (2) ◽

pp. 712-720 ◽

Cited By ~ 56

Author(s):

Minna M. Hämäläinen ◽

G. F. Gebhart ◽

Timothy J. Brennan

Keyword(s):

Receptive Field ◽

Background Activity ◽

Response Magnitude ◽

Field Size ◽

Response Threshold ◽

Mechanical Stimuli ◽

Receptive Field Size ◽

C Fibers ◽

Afferent Fibers ◽

Aβ Fibers

The purpose of this study was to examine which primary afferent fibers are sensitized to mechanical stimuli after an experimental surgical incision to the glabrous skin of the rat hindpaw. Afferent fibers teased from the L5dorsal root or the tibial nerve were recorded in anesthetized rats. The mechanical response properties of each fiber were characterized before and 45 min after an incision (or sham procedure) within the mechanical receptive field. Sensitization is characterized by an expansion of the mechanical receptive field, an increase in background activity, an increase in response magnitude, or a decrease in response threshold. After incision, the background activity and response properties of Aβ-fibers ( n = 9) to mechanical stimuli were unchanged. Four of 13 mechanosensitive Aδ-fibers exhibited sensitization after the incision; response threshold decreased, response magnitude increased, or receptive field size increased. Background activity of Aδ-fibers was not increased by the incision. Sensitization was observed in 4 of 18 mechanosensitive C-fibers 45 min after the incision. Background activity of C-fibers was not increased by the incision. In a group of mechanically insensitive afferent fibers (MIAs), 3 of 7 Aδ-fibers and 4 of 10 C-fibers sensitized 45 min after incision. Response threshold was decreased in only 2 of 17 MIAs; receptive field size increased in 7 of 17 MIAs. Aβ-fibers did not sensitize after the incision, and only 8 of 31 (26%) mechanosensitive Aδ- and C-fibers gave evidence of sensitization. In a group of MIA Aδ- and C-fibers, a greater percentage of 17 fibers studied (41%) were sensitized after incision. In this model, the principal effect of an incision, when examined 45 min after the insult, is an increase in receptive field size of the afferents, particularly those characterized as MIAs. To the extent that the mechanical hyperalgesia characterized in the same model is initiated in the periphery, it would appear that spatial summation of modestly increased response magnitude is important to the development of hyperalgesia.

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Receptive Field Size and Response Latency Are Correlated Within the Cat Visual Thalamus

Journal of Neurophysiology ◽

10.1152/jn.00847.2004 ◽

2005 ◽

Vol 93 (6) ◽

pp. 3537-3547 ◽

Cited By ~ 20

Author(s):

Chong Weng ◽

Chun-I Yeh ◽

Carl R. Stoelzel ◽

Jose-Manuel Alonso

Keyword(s):

Receptive Field ◽

Spatial Frequency ◽

Response Latency ◽

Time Course ◽

Frequency Tuning ◽

Receptive Fields ◽

Cortical Cell ◽

Field Size ◽

Receptive Field Size ◽

Spatial Frequency Tuning

Each point in visual space is encoded at the level of the thalamus by a group of neighboring cells with overlapping receptive fields. Here we show that the receptive fields of these cells differ in size and response latency but not at random. We have found that in the cat lateral geniculate nucleus (LGN) the receptive field size and response latency of neighboring neurons are significantly correlated: the larger the receptive field, the faster the response to visual stimuli. This correlation is widespread in LGN. It is found in groups of cells belonging to the same type (e.g., Y cells), and of different types (i.e., X and Y), within a specific layer or across different layers. These results indicate that the inputs from the multiple geniculate afferents that converge onto a cortical cell (approximately 30) are likely to arrive in a sequence determined by the receptive field size of the geniculate afferents. Recent studies have shown that the peak of the spatial frequency tuning of a cortical cell shifts toward higher frequencies as the response progresses in time. Our results are consistent with the idea that these shifts in spatial frequency tuning arise from differences in the response time course of the thalamic inputs.

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Quantitative effects of GABA and bicuculline methiodide on receptive field properties of neurons in real and simulated whisker barrels

Journal of Neurophysiology ◽

10.1152/jn.1996.75.2.547 ◽

1996 ◽

Vol 75 (2) ◽

pp. 547-560 ◽

Cited By ~ 88

Author(s):

H. T. Kyriazi ◽

G. E. Carvell ◽

J. C. Brumberg ◽

D. J. Simons

Keyword(s):

Receptive Field ◽

Time Course ◽

Response Magnitude ◽

Gabab Receptors ◽

Field Size ◽

Percentage Increase ◽

Gamma Aminobutyric Acid ◽

Receptive Field Size ◽

Bicuculline Methiodide ◽

Receptive Field Properties

1. Carbon fiber multibarrel glass microelectrodes were used to record extracellular single-unit activity during microiontophoretic application of gamma-aminobutyric acid (GABA) or bicuculline methiodide (BMI) onto layer IV barrel neurons in the somatosensory cortex of fentanyl-sedated rats. Excitatory and inhibitory aspects of the neurons' receptive fields were quantified with the use of controlled whisker stimuli. The principally activating whisker and one of its immediately adjacent neighbors were deflected alone or in paired combinations involving a condition-test paradigm. 2. Units were distinguished electrophysiologically on the basis of the time course of their action potential waveforms. Data were obtained from 26 regular-spike units (RSUs; presumed spiny stellate cells) and 7 fast-spike units (FSUs; presumed GABAergic neurons). An average of 15.0 nA of GABA produced a one-third to one-half reduction in RSU responses evoked by the maximally effective stimulus. An average of 8.7 nA of BMI was needed to counteract this reduction. This amount of BMI, in the absence of exogenous GABA, was found to increase average RSU and FSU responses by 98 and 53%, respectively, relative to predrug levels. 3. For RSUs, the BMI-induced twofold increase in responses evoked by moving the principal whisker at the neuron's best deflection angle was accompanied by an almost threefold increase in responses evoked by similarly moving an adjacent whisker. Disproportionately large percentage increases were also seen for responses to nonpreferred directions of principal and adjacent whisker movement. BMI thus effectively increased receptive field size and decreased angular tuning. Similarly, responses to stimulus offsets, which are normally smaller than ON responses, were increased proportionally more. 4. Predrug responses of FSUs were more vigorous than those of RSUs. However, FSUs showed a similar inverse relationship between percentage increase with BMI and initial response magnitude, although the proportional increases were less pronounced. 5. GABA, like BMI, had the greatest proportional effects on those responses that were initially smallest. It produced results opposite those of BMI, effectively decreasing receptive field size and sharpening angular tuning. 6. A previously described computational model of a barrel was tested for its ability to reproduce quantitatively the effects of BMI and GABA. The application of BMI was simulated by decreasing the strength of the inhibitory inputs onto the particular cell under study in the model network. GABA microiontophoresis was simulated by adding a constant hyperpolarizing voltage. The model RSUs and FSUs displayed proportional changes in response magnitude that were quantitatively similar to those of their biological counterparts. 7. Surround inhibition was greatly attenuated by BMI application, both for the real and simulated barrel neurons. Disinhibition was less pronounced for the former, perhaps because, unlike the simulated neurons, they also possess GABAB receptors, which are unaffected by BMI. 8. We conclude that the inhibitory receptive field properties of barrel neurons can be explained by intrabarrel inhibition and that the expansion of receptive field size and loss of angular tuning with BMI is due to an enhanced effectiveness of convergent, multi-whisker thalamocortical input. Examination of the model neurons' behavior suggests that the altered activity in response to GABA or BMI application, respectively, can be explained by the nonlinear effects of shifting somal membrane potential away from or toward the neuron's firing threshold.

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ENLARGEMENT OF THE RECEPTIVE FIELD SIZE TO LOW INTENSITY MECHANICAL STIMULATION IN THE RAT SPINAL NERVE LIGATION MODEL OF NEUROPATHY

Journal of the Peripheral Nervous System ◽

10.1046/j.1529-8027.2000.00022-48.x ◽

2000 ◽

Vol 5 (4) ◽

pp. 248-248

Author(s):

R Suzuki ◽

Vk Kontinen ◽

E Matthews ◽

E Williams ◽

Ah Dickenson

Keyword(s):

Receptive Field ◽

Mechanical Stimulation ◽

Spinal Nerve ◽

Spinal Nerve Ligation ◽

Field Size ◽

Receptive Field Size ◽

Low Intensity

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Changes in the response properties of neurons in the ventroposterior lateral thalamic nucleus of the raccoon after peripheral deafferentation

Journal of Neurophysiology ◽

10.1152/jn.1996.75.6.2441 ◽

1996 ◽

Vol 75 (6) ◽

pp. 2441-2450 ◽

Cited By ~ 62

Author(s):

D. D. Rasmusson

Keyword(s):

Receptive Field ◽

Thalamic Nucleus ◽

Receptive Fields ◽

Field Size ◽

Mechanical Stimuli ◽

Sensory Pathways ◽

Average Latency ◽

Somatotopic Map ◽

Almost All ◽

Stimulation Of

1. Single neurons in the ventroposterior lateral thalamic nucleus were studied in 10 anesthetized raccoons, 4 of which had undergone amputation of the fourth digit 4-5 mo before recording. Neurons with receptive fields on the glabrous skin of a forepaw digit were examined in response to electrical stimulation of the “on-focus” digit that contained the neuron's receptive field and stimulation of an adjacent, “off-focus” digit. 2. In normal raccoons all neurons responded to on-focus stimulation with an excitation at a short latency (mean 13 ms), whereas only 63% of the neurons responded to off-focus digit stimulation. The off-focus responses had a longer latency (mean 27.2 ms) and a higher threshold than the on-focus responses (800 and 452 microA, respectively). Only 3 of 32 neurons tested with off-focus stimulation had both a latency and a threshold within the range of on-focus values. Inhibition following the excitation was seen in the majority of neurons with both types of stimulation. 3. In the raccoons with digit removal, the region of the thalamus that had lost its major peripheral input (the “deafferented” region) was distinguished from the normal third and fifth digit regions on the basis of the sequence of neuronal receptive fields within a penetration and receptive field size as described previously. 4. Almost all of the neurons in the deafferented region (91%) were excited by stimulation of one or both adjacent digits. The average latency for these responses was shorter (15.3 ms) and the threshold was lower than was the case with off-focus stimulation in control animals. These values were not significantly different from the responses to on-focus stimulation in the animals with digit amputation. 5. These results confirm that reorganization of sensory pathways can be observed at the thalamic level. In addition to the changes in the somatotopic map that have been shown previously with the use of mechanical stimuli, the present paper demonstrates an improvement in several quantitative measures of single-unit responses. Many of these changes suggest that this reorganization could be explained by an increased effectiveness of preexisting, weak connections from the off-focus digits; however, the increase in the proportion of neurons responding to stimulation of adjacent digits may indicate that sprouting of new connections also occurs.

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