Synaptic enhancement and enhanced excitability in presynaptic and postsynaptic neurons in the conditioned stimulus pathway of Hermissenda.

Identified type A photoreceptors of Hermissenda express differential effects of classical conditioning. Lateral type A photoreceptors exhibit an increase in excitability to both the conditioned stimulus (CS; light) and extrinsic current. In contrast, medial type A photoreceptors do not express enhanced excitability, but do show enhancement of the medial B to medial A synaptic connection. Therefore, both enhanced excitability and changes in synaptic strength may contribute to long-term plasticity underlying classical conditioning. The activation of protein kinase C (PKC) is involved in the induction of enhanced excitability of identified type B photoreceptors produced by one-trial conditioning and the expression of enhanced excitability in B photoreceptors after multitrial classical conditioning. We have examined a possible role for persistent kinase activity in the expression of enhanced excitability in lateral type A photoreceptors and enhancement of the medial B to medial type A synaptic connection after classical conditioning. Injection of the PKC inhibitor peptide PKC(19-36) into medial type B photoreceptors of conditioned animals did not significantly change the amplitude of medial A IPSPs elicited by single spikes in the medial B photoreceptor. Injections of PKC(19-36) into medial B photoreceptors of pseudorandom controls also did not significantly change the amplitude of IPSPs recorded from the medial A photoreceptor. In contrast, spikes elicited by extrinsic current in lateral type A photoreceptors of conditioned animals were significantly reduced in frequency after intracellular injection of PKC(19-36) as compared with pseudorandom controls. Injection of the noninhibitory analog peptide [glu27]PKC(19-36) did not affect excitability. Thus, enhanced excitability in the lateral A photoreceptor of conditioned animals seems to be influenced, in part, by a constitutively active kinase or a persistent kinase activator, whereas synaptic enhancement of the connection between the medial B and medial A photoreceptors of conditioned animals may involve a different mechanism.

The effect of medial frontal cortex lesions on cardiovascular conditioned emotional responses in the rat.

The effect of ventral medial frontal cortex (MFC) lesions on heart rate and blood pressure during conditioned emotional responses (CER) was investigated. Male Sprague-Dawley rats were divided into two groups: MFC-lesioned rats (n = 11) sustained bilateral lesions of the infralimbic and ventral prelimbic regions of the MFC via microinjection of the neurotoxin N-methyl-D-aspartate; Controls (n = 13) received sterile saline. Following a 2-week recovery period, all animals were trained; one of two tones served as the conditioned stimulus (CS) and a 2 mA footshock served as the unconditioned stimulus (US). The CS+ tone was consistently paired with the US, while the CS- tone was randomly paired with the US. Heart rate and blood pressure were recorded during CS+ and CS- presentations before and after administration of the following pharmacological agents: atropine, atenolol, and atropine + atenolol. All animals responded to the CS+ with increased BP compared to baseline; the increase was not significantly different between groups. Controls responded to the CS+ with increased HR, while MFC-lesioned animals displayed a bimodal HR response which was not significantly different from baseline, but was significantly different from Controls. Pharmacological blockade of the HR response revealed coactivation of the sympathetic and parasympathetic nervous systems during the CS+, with a significant decrease (52%) in the sympathetic tachycardia component of the CS+ HR response in MFC-lesioned rats as compared to Controls; the parasympathetic bradycardia component was not altered by MFC lesions. In all cases, CS- responses were smaller than the CS+ responses. Pharmacological analysis revealed that the CS- HR response was mediated by the sympathetic component only, which was also significantly reduced in MFC-lesioned animals as compared to Controls. This significant reduction in the sympathetically mediated HR component of both the reinforced CER (CS+) and the unreinforced CER (CS-) following ventral MFC lesions implies that the MFC is necessary for complete sympathetic activation of cardiovascular responses to both severely and mildly stressful stimuli. The role of the MFC in emotion is also discussed.

Enhancement of type B and A photoreceptor inhibitory synaptic connections in conditioned Hermissenda.

Intrinsic changes have been identified in isolated and intact type A and type B photoreceptors following classical conditioning of the nudibranch mollusk Hermissenda. Aspects of various intrinsic, nonsynaptic modifications are expressed by alterations in the excitability of identified photoreceptors in response to the conditioned stimulus. In addition to changes in cellular excitability, changes in synaptic strength between identified neurons have been proposed as a possible mechanism of associative learning in several invertebrate preparations. Here we report that classical conditioning produces differential effects upon the strength of inhibitory monosynaptic connections between identified pairs of type B and type A photoreceptors. The amplitude of IPSPs elicited by an action potential in the medial type B photoreceptor and recorded from medical type A photoreceptors was significantly enhanced in conditioned animals as compared to pseudorandom controls. In contrast, the amplitude of IPSPs elicited by an action potential in the lateral type B photoreceptor and recorded from lateral type A photoreceptors did not show significant synaptic enhancement following conditioning. These results provide additional evidence for differential effects of conditioning upon cellular modifications in identified type A and type B photoreceptors, and further indicate that multiple sites of cellular plasticity exist in the visual system of conditioned Hermissenda.

Differential expression of correlates of classical conditioning in identified medial and lateral type A photoreceptors of Hermissenda.

Classical conditioning of Hermissenda produces neurophysiological correlates in the primary sensory neurons of the pathway mediating the conditioned stimulus (CS), the type B and type A photoreceptors. Biophysical and biochemical changes intrinsic to the type B photoreceptors have been studied extensively in conditioned animals. A second site for intrinsic modification with learning has been recently identified in type A photoreceptors. We have recorded from identified medial and lateral type A photoreceptors in conditioned animals and animals that received pseudorandom presentations of light (CS) and rotation (unconditioned stimulus). Here we report that conditioning produces differential effects upon CS-elicited spike frequency and intrinsic excitability detected in identified lateral and medial type A photoreceptors. Lateral type A photoreceptors from conditioned animals exhibited significant increases in spike frequency elicited by the CS as compared to pseudorandom controls. In contrast, CS-elicited spike frequency recorded in medial type A photoreceptors was not significantly different from random controls. The amplitude of the peak and plateau phases of the generator potential of medial and lateral type A photoreceptors was decreased in conditioned animals as compared to random controls. In addition, only lateral type A photoreceptors exhibited enhanced cellular excitability as expressed by increased spike discharges produced by the injection of extrinsic depolarizing current pulses. Conditioning also decreased spike frequency accommodation in lateral type A photoreceptors. In normal controls, medial type B photoreceptors produced stronger synaptic inhibition of medial type A photoreceptors than the lateral type B photoreceptors inhibition of lateral type A photoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of medial frontal cortex lesions on respiration, "freezing," and ultrasonic vocalizations during conditioned emotional responses in rats.

The effect of ventral medial frontal cortex (MFC) lesions on respiratory rate (RESP), immobility ("freezing"), and ultrasonic vocalizations (USVs) during conditioned emotional responses (CERs) was investigated. Male Sprague-Dawley rats were divided into two groups: MFC-lesioned rats (N = 11) sustained bilateral lesions of the infralimbic region of the MFC via microinjection of the neurotoxin NMDA; controls received sterile saline. Following a 2 week recovery period, all animals were differentially conditioned to two tones; a 2 mA footshock served as the unconditioned stimulus (US). The CS+tone was consistently paired with the US, while the CSr tone was randomly paired with the US. On the following day, RESP, freezing, and USVs were recorded during CER testing (no US were presented). All animals responded during the CS+ with increased RESP compared to baseline; the increase in MFC rats was significantly larger than in controls. All animals also froze at the onset of the CS+. Following the CS+, controls displayed a prolonged period of freezing (265 +/- 37 sec) and decreased RESP compared to baseline, and 92% emitted USVs. In contrast, MFC rats displayed a significantly shorter period of freezing (86 +/- 25 sec) and little or no USV; RESP remained significantly elevated throughout the remainder of the trial. These behaviors indicate a significantly altered stress response following ventral MFC lesions, implying that the MFC may be necessary for complete expression of various behavioral responses to "stressful" stimuli. The role of the MFC in emotion is also discussed.

Functional mapping of the rat brain during vocalizations: a 2-deoxyglucose study.

Autoradiographic [14C]2-deoxyglucose (2-DG) procedures were used to map the functional activity in the CNS during vocalizations elicited by electrical stimulation of the midbrain reticular formation (MRF) in behaving rats. Following injection of 2-DG, rats received MRF stimulation through stainless steel electrodes over 90 min. Yoked controls received 2-DG injection followed by playback of the recorded vocalizations. Relative differences in peak isotope uptake (gray/white matter ratios) in 22 structures related to vocalization were compared between the two groups. The major findings were localized to hypothalamus, midbrain and brainstem structures. Significant increases in 2-DG uptake were noted in the following structures in MRF stimulated rats: dorsolateral central gray (PAG), MRF, lateral hypothalamus (LH), ventromedial hypothalamus (VmH), paraventricular nucleus (PVN) and nucleus ambiguus (NA). Cortical structures were not activated during MRF stimulation. The PAG and NA are known to be important relays in the production of vocalizations. MRF stimulation, therefore, activates the motor output pathways for vocalization, but does not appear to activate cortical and limbic motivational centers.