Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial.

Although individuals with autism are known to have significant communication problems, the cellular mechanisms responsible for impaired communication are poorly understood. Valproic acid (VPA) is an anticonvulsant that is a known risk factor for autism in prenatally exposed children. Prenatal VPA exposure in rats causes numerous neural and behavioral abnormalities that mimic autism. We predicted that VPA exposure may lead to auditory processing impairments which may contribute to the deficits in communication observed in individuals with autism. In this study, we document auditory cortex responses in rats prenatally exposed to VPA. We recorded local field potentials and multiunit responses to speech sounds in primary auditory cortex, anterior auditory field, ventral auditory field. and posterior auditory field in VPA exposed and control rats. Prenatal VPA exposure severely degrades the precise spatiotemporal patterns evoked by speech sounds in secondary, but not primary auditory cortex. This result parallels findings in humans and suggests that secondary auditory fields may be more sensitive to environmental disturbances and may provide insight into possible mechanisms related to auditory deficits in individuals with autism.

Individuals with SHANK3 mutations have severely impaired language abilities, yet the auditory cortex response to sound has remained largely understudied. In this study, we found that auditory cortex responses were weaker and were unable to respond well to rapid sounds in Shank3-deficient rats compared to control rats. The rat model of the auditory impairments in SHANK3 mutation could be used to test potential rehabilitation or drug therapies to improve the communication impairments observed in individuals with Phelan-McDermid syndrome.

Facilitation of Pavlovian conditioned cardiodecelerations following preshock in immobilized rats. PHYSIOL. BEHAV. 15(6) 653-658, 1975. -Two experiments are reported that examine the effects of unsignalled, inescapable prior shock exposure (PSE) on shock-motivated Pavlovian conditioned heart rate (HR) decelerations in rats. Both studies involved 2 CS-US contingencies (paired and unpaired) and 2 preshock treatments (preshock and no preshock). The 2 designs differed in the type of immobilization procedures to which the rats were submitted and the number of conditioning sessions. In Experiment 1 rats were conditioned for 2 consecutive 35 trial sessions while physically restrained, whereas only one conditioning session was used in Experiment 2 on animals that were paralyzed with d-tubocurarine chloride (dTC). The results demonstrated that PSE augmented the magnitude of the HR conditioned response (CR) in both the physically restrained and paralyzed preparations. In addition, PSE improved the rate of acquisition of the conditioned cardiodeceleration in physically restrained rats and tended to facilitate reinstatement of the HR CR during the second conditioning session. These data support the notion that certain nonspecific stress processes that are relatively independent of the CS-US contingency but related to the occurrence of response suppression are intimately involved in Pavlovian HR conditioning.

his experiment examined the influence of plasma corticosterone on stress-induced ulceration in restrained rats. Gastric pathology and plasma corticosterone levels were examined in normal (UNOP) and adrenalectomized (ADX) rats under two conditions of shock predictability. The severity of the gastric ulceration in unoperated rats given noncontingent presentations of a tone and an electric shock was greater than in subjects receiving shocks contingent upon CS presentation. When ulcer pathology was evaluated for ADX animals, no differences were found between the predictable and the unpredictable shock groups. The results were discussed in terms of the necessary and sufficient conditions for stomach ulcer formation as a function of shock predictability and restraint stress and the necessity to investigate alternative hypotheses. Recent evidence has suggested that several physiological mechanisms contribute to gastric ulcer formation in restrained rats. Weiss (1968; 1970) has