Development of Reorganization of the Auditory Cortex Caused by Fear Conditioning: Effect of Atropine

2003 ◽  
Vol 90 (3) ◽  
pp. 1904-1909 ◽  
Author(s):  
Weiqing Ji ◽  
Nobuo Suga

Reorganization of the frequency map in the central auditory system is based on shifts in the best frequencies (BFs; hereafter, BF shifts), together with the frequency-response curves, of auditory neurons. In the big brown bat, conditioning with acoustic stimulation followed by electric leg-stimulation causes BF shifts of collicular and cortical neurons. The collicular BF shift develops quickly and is short term, whereas the cortical BF shift develops slowly and is long term. The acetycholine level in the auditory cortex must be high during conditioning to develop these BF shifts. We studied the effect of atropine (an antagonist of muscarinic acetylcholine receptors) applied to the auditory cortex on the development of the long-term cortical BF shift in the awake bat caused by a 30-min conditioning session. We found 1) the cortical BF shift starts to develop ∼15 min after the onset of the conditioning, gradually increases over 60 min, and reaches a plateau, 2) the cortical BF shift changes from short to long term ∼45 min after the onset of the conditioning, 3) the cortical BF shift can plateau at different frequencies between the BF of a given neuron in the control condition and the frequency of the conditioning tone, 4) the maximum BF shift is determined ∼70 min after the onset of the conditioning, and 5) acetylcholine plays an important role in the development of the cortical BF shift. Its role ends ∼180 min after the onset of the conditioning.

2004 ◽  
Vol 92 (6) ◽  
pp. 3192-3199 ◽  
Author(s):  
Xiaofeng Ma ◽  
Nobuo Suga

Repetitive acoustic stimulation, auditory fear conditioning, and focal electric stimulation of the auditory cortex (AC) each evoke the reorganization of the central auditory system. Our current study of the big brown bat indicates that focal electric stimulation of the AC evokes center-surround reorganization of the frequency map of the AC. In the center, the neuron's best frequencies (BFs), together with their frequency–tuning curves, shift toward the BFs of electrically stimulated cortical neurons (centripetal BF shifts). In the surround, BFs shift away from the stimulated cortical BF (centrifugal BF shifts). Centripetal BF shifts are much larger than centrifugal BF shifts. An antagonist (bicuculline methiodide) of inhibitory synaptic transmitter receptors changes centrifugal BF shifts into centripetal BF shifts, whereas its agonist (muscimol) changes centripetal BF shifts into centrifugal BF shifts. This reorganization of the AC thus depends on a balance between facilitation and inhibition evoked by focal cortical electric stimulation. Unlike neurons in the AC of the big brown bat, neurons in the Doppler-shifted constant-frequency (DSCF) area of the AC of the mustached bat are highly specialized for fine-frequency analysis and show almost exclusively centrifugal BF shifts for focal electric stimulation of the DSCF area. Our current data indicate that in the highly specialized area, lateral inhibition is strong compared with the less-specialized area and that the specialized and nonspecialized areas both share the same inhibitory mechanism for centrifugal BF shifts.


2005 ◽  
Vol 94 (4) ◽  
pp. 2676-2682 ◽  
Author(s):  
Yongkui Zhang ◽  
Nobuo Suga

Focal electric stimulation of the auditory cortex, 30-min repetitive acoustic stimulation, and auditory fear conditioning each evoke shifts of the frequency-tuning curves [hereafter, best frequency (BF) shifts] of cortical and collicular neurons. The short-term collicular BF shift is produced by the corticofugal system and primarily depends on the relationship in BF between a recorded collicular and a stimulated cortical neuron or between the BF of a recorded collicular neuron and the frequency of an acoustic stimulus. However, it has been unknown whether focal electric stimulation of the inferior colliculus evokes the collicular BF shift and whether the collicular BF shift, if evoked, depends on corticofugal feedback. In our present research with the awake big brown bat, we found that focal electric stimulation of collicular neurons evoked the BF shifts of collicular neurons located near the stimulated ones; that there were two types of BF shifts: centripetal and centrifugal BF shifts, i.e., shifts toward and shifts away from the BF of stimulated neurons, respectively; and that the development of these collicular BF shifts was blocked by inactivation of the auditory cortex. Our data indicate that the collicular BF shifts (plasticity) evoked by collicular electric stimulation depended on corticofugal feedback. It should be noted that collicular BF shifts also depend on acetylcholine because it has been demonstrated that atropine (an antagonist of muscarinic acetylcholine receptors) applied to the IC blocks the development of collicular BF shifts.


2000 ◽  
Vol 83 (4) ◽  
pp. 1856-1863 ◽  
Author(s):  
Syed A. Chowdhury ◽  
Nobuo Suga

In a search phase of echolocation, big brown bats, Eptesicus fuscus, emit biosonar pulses at a rate of 10/s and listen to echoes. When a short acoustic stimulus was repetitively delivered at this rate, the reorganization of the frequency map of the primary auditory cortex took place at and around the neurons tuned to the frequency of the acoustic stimulus. Such reorganization became larger when the acoustic stimulus was paired with electrical stimulation of the cortical neurons tuned to the frequency of the acoustic stimulus. This reorganization was mainly due to the decrease in the best frequencies of the neurons that had best frequencies slightly higher than those of the electrically stimulated cortical neurons or the frequency of the acoustic stimulus. Neurons with best frequencies slightly lower than those of the acoustically and/or electrically stimulated neurons slightly increased their best frequencies. These changes resulted in the over-representation of repetitively delivered acoustic stimulus. Because the over-representation resulted in under-representation of other frequencies, the changes increased the contrast of the neural representation of the acoustic stimulus. Best frequency shifts for over-representation were associated with sharpening of frequency-tuning curves of 25% of the neurons studied. Because of the increases in both the contrast of neural representation and the sharpness of tuning, the over-representation of the acoustic stimulus is accompanied with an improvement of analysis of the acoustic stimulus.


2021 ◽  
pp. 0271678X2110103
Author(s):  
Nao Hatakeyama ◽  
Miyuki Unekawa ◽  
Juri Murata ◽  
Yutaka Tomita ◽  
Norihiro Suzuki ◽  
...  

A variety of brain cells participates in neurovascular coupling by transmitting and modulating vasoactive signals. The present study aimed to probe cell type-dependent cerebrovascular (i.e., pial and penetrating arterial) responses with optogenetics in the cortex of anesthetized mice. Two lines of the transgenic mice expressing a step function type of light-gated cation channel (channelrhodopsine-2; ChR2) in either cortical neurons (muscarinic acetylcholine receptors) or astrocytes (Mlc1-positive) were used in the experiments. Photo-activation of ChR2-expressing astrocytes resulted in a widespread increase in cerebral blood flow (CBF), extending to the nonstimulated periphery. In contrast, photo-activation of ChR2-expressing neurons led to a relatively localized increase in CBF. The differences in the spatial extent of the CBF responses are potentially explained by differences in the involvement of the vascular compartments. In vivo imaging of the cerebrovascular responses revealed that ChR2-expressing astrocyte activation led to the dilation of both pial and penetrating arteries, whereas ChR2-expressing neuron activation predominantly caused dilation of the penetrating arterioles. Pharmacological studies showed that cell type-specific signaling mechanisms participate in the optogenetically induced cerebrovascular responses. In conclusion, pial and penetrating arterial vasodilation were differentially evoked by ChR2-expressing astrocytes and neurons.


Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5185-5194 ◽  
Author(s):  
Dinesh Gautam ◽  
Inigo Ruiz de Azua ◽  
Jian Hua Li ◽  
Jean-Marc Guettier ◽  
Thomas Heard ◽  
...  

Previous studies have shown that β-cell M3 muscarinic acetylcholine receptors (M3Rs) play a key role in maintaining blood glucose homeostasis by enhancing glucose-dependent insulin release. In this study, we tested the hypothesis that long-term, persistent activation of β-cell M3Rs can improve glucose tolerance and ameliorate the metabolic deficits associated with the consumption of a high-fat diet. To achieve the selective and persistent activation of β-cell M3Rs in vivo, we generated transgenic mice that expressed the Q490L mutant M3R in their pancreatic β-cells (β-M3-Q490L Tg mice). The Q490L point mutation is known to render the M3R constitutively active. The metabolic phenotypes of the transgenic mice were examined in several in vitro and in vivo metabolic tests. In the presence of 15 mm glucose and the absence of M3R ligands, isolated perifused islets prepared from β-M3-Q490L Tg mice released considerably more insulin than wild-type control islets. This effect could be completely blocked by incubation of the transgenic islets with atropine (10 μm), an inverse muscarinic agonist, indicating that the Q490L mutant M3R exhibited ligand-independent signaling (constitutive activity) in mouse β-cells. In vivo studies showed that β-M3-Q490L Tg mice displayed greatly improved glucose tolerance and increased serum insulin levels as well as resistance to diet-induced glucose intolerance and hyperglycemia. These results suggest that chronic activation of β-cell M3Rs may represent a useful approach to boost insulin output in the long-term treatment of type 2 diabetes.


2004 ◽  
Vol 91 (1) ◽  
pp. 301-313 ◽  
Author(s):  
Thomas Lu ◽  
Xiaoqin Wang

The present study explores the issue of cortical coding by spike count and timing using statistical and information theoretic methods. We have shown in previous studies that neurons in the auditory cortex of awake primates have an abundance of sustained discharges that could represent time-varying signals by temporal discharge patterns or mean firing rates. In particular, we found that a subpopulation of neurons can encode rapidly occurring sounds, such as a click train, with discharges that are not synchronized to individual stimulus events, suggesting a temporal-to-rate transformation. We investigated whether there were stimulus-specific temporal patterns embedded in these seemingly random spike times. Furthermore, we quantitatively analyzed the precision of spike timing at stimulus onset and during ongoing acoustic stimulation. The main findings are the following. 1) Temporal and rate codes may operate at separate stimulus domains or encode the same stimulus domain in parallel via different neuronal populations. 2) Spike timing was crucial to encode stimulus periodicity in “synchronized” neurons. 3) “Nonsynchronized” neurons showed little stimulus-specific spike timing information in their responses to time-varying signals. Such responses therefore represent processed (instead of preserved) information in the auditory cortex. And 4) spike timing on the occurrence of acoustic events was more precise at the first event than at successive ones and more precise with sparsely distributed events (longer time intervals between events) than with densely packed events. These results indicate that auditory cortical neurons mark sparse acoustic events (or onsets) with precise spike timing and transform rapidly occurring acoustic events into firing rate-based representations.


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