Learning-related cellular modifications were studied in the rat piriform cortex. Water-deprived rats were divided to three groups: 'trained' rats were trained in a four-arm maze to discriminate positive cues in pairs of odours, 'control' rats were 'pseudo-trained' by random water rewarding, and 'naive' rats were water-deprived only. In one experimental paradigm, the trained group was exposed to extensive training with rats learning to discriminate between 35 and 50 pairs of odours. Piriform cortex pyramidal neurons from 'trained', 'control' and 'naive' rats did not differ in their passive membrane properties and single spike characteristics. However, the after-hyperpolarizations (AHPs) that follow six-spike trains were reduced after 'extensive training' by 43% and 36% compared with 'control' and 'naive', respectively. This effect was not observed in the piriform cortex of another group of rats, in which hyperexcitability was induced by chemical kindling. In another experimental paradigm rats were trained only until they demonstrated 'rule learning', usually after discriminating between one and two pairs of odours ('mild training'). In this experiment, a smaller, yet significant, reduction (20%) in AHPs was observed. AHP reduction was apparent in most of the sampled neurons. AHP remained reduced up to 3 days after the last training session. 5 days or more after the last training session, AHP amplitude recovered to pre-training value and did not differ between 'trained' rats and the others. Accordingly, training suspension for 5 days or more resulted in slower learning of novel odours. We suggest that increased neuronal excitability, manifested as reduced AHP, is related to the ability of the cortical network to enter a 'learning mode' which creates favourable conditions for enhanced learning capability.

We studied the role of acetylcholine (ACh) in creating learningrelated long-lasting modifications in the rat cortex. Rats were trained to discriminate positive and negative cues in pairs of odors, until they demonstrated rule learning and entered a mode of high capability for learning of additional odors. We have previously reported that pyramidal neurons in olfactory (piriform) cortex from trained rats had reduced spike afterhyperpolarization (AHP) for 3 d after rule learning. In the present study we examined the mechanism underlying this long-lasting modification. The cholinergic agonist carbachol reduced both slow AHP and firing adaptation in neurons from pseudotrained rats, but had no effect on neurons from trained rats, suggesting pre-existing cholinergic effect. Intracellular application of the calcium chelator BAPTA abolished the difference in slow AHP and in adaptation between groups, suggesting that the difference resulted from reduction in the ACh-sensitive, Ca 2ϩ -dependent potassium current, I AHP . At the behavioral level, application of the muscarinic blocker scopolamine before each training session delayed rule learning but had no effect on further acquisition of odor memory. We suggest that intense ACh activity during rule learning enhances neuronal excitability in the piriform cortex by reducing I AHP and that the effect outlasts the stage of rule learning, so that ACh activity is not crucial for further odor learning.

Learning-related cellular modifications were studied in the rat piriform cortex after operand conditioning. Rats were trained to discriminate positive cues in pairs of odors. In one experimental paradigm, rats were trained to memorize 35-50 pairs of odors ("extensive training"). In another paradigm, training was continued only until rats acquired the rule of the task, usually after learning the first two pairs of odors ("short training"). "Pseudotrained" and "naive" rats served as controls. We have previously shown that "rule learning" of this task was accompanied by reduced spike afterhyperpolarization in pyramidal neurons in brain slices of the piriform cortex. In the present study, synaptic inputs to the same cells were examined. Pairs of electrical stimuli applied to the intrinsic fibers that interconnect layer II pyramidal neurons revealed significant reduction in paired-pulse facilitation (PPF) in this pathway even after short training. PPF in shortly trained rats was reduced to the same extent as in extensively trained rats. PPF reduction did not result from modification of membrane properties in the postsynaptic cells, change in postsynaptic inhibition, or impairment of the facilitation mechanism. Extracellular field potential recordings showed enhanced synaptic transmission in these synapses. The reduction in PPF became apparent only 3 d after task acquisition and returned to control value 5 d later. PPF evoked by stimulating the afferent fibers to the same neurons was increased 1 d after training for 2 d. We suggest that the transient enhancement in connectivity in the intrinsic pathway is related to the enhanced learning capability and not to memory for specific odors, which lasts for weeks.

SUMMARY1. Propagation of action potentials at high frequency was studied in a branching axon of the lobster by means of simultaneous intracellular recording both before and after the branch point.2. Although the branching axon studied has a geometrical ratio close to one (perfect impedance matching) conduction across the branch point failed at stimulation frequencies above 30 Hz.3. The block of conduction after high frequency stimulation occurred at the branch point per se. The parent axon and daughter branches continued to conduct action potentials. 4. Conduction block after high frequency stimulation appeared first in the thicker daughter branch and only later in the thin branch.5. With high frequency stimulation there was a 10-15 % reduction in amplitude of the action potential in the parent axon, a corresponding decrease in the rate of rise ofthe action potential, a 25-30 % decrease in conduction velocity, marked increase in threshold and prolongation of the refractory period. In addition the membrane was depolarized by 1-3 mV.6. Measurements of the membrane current using the patch clamp technique showed a large decrease in the phase of inward current associated with the action potential, before the branching point.7. The small membrane depolarization seen after high frequency stimulation is not the sole cause of the conduction block. Imposed prolonged membrane depolarization (8 mV for 120 sec) was insufficient to produce conduction block.8. In vivo chronic extracellular recordings from the main nerve bundle (which contains the parent axon) and the large daughter branch revealed that: (a) the duration and frequency of trains of action potentials along the axons exceeded those used in the isolated nerve experiments and (b) conduction failure in the large daughter branch could be induced in the whole animal by electrical stimulation of the main branch as in the isolated preparation.9. Possible mechanisms underlying block of conduction after high frequency stimulation in a branching axon are discussed.

We studied the effect of olfactory learning-induced modifications in piriform (olfactory) cortex pyramidal neurons on the propagation of postsynaptic potentials (PSPs). Rats were trained to distinguish between odors in pairs, in an olfactory discrimination task. Three days after training completion, PSPs were evoked in layer II pyramidal cells in piriform cortex brain slices by electrical stimulation of two pathways. Stimulation of layer Ib activated the intra-cortical fibers that terminate on the proximal region of the apical and basal dendrites. Stimulation of layer Ia activated the afferent axons that originate from the olfactory bulb and terminate on the distal apical dendrites. We have previously shown that olfactory training is accompanied by enhanced synaptic transmission in the intrinsic pathway, but not in the afferent pathway at 3 days after training. Here we show that at this stage, in both pathways PSPs evoked in neurons from trained rats had significantly faster rise time measured at the soma compared with PSPs in neurons from pseudo-trained and naive rats. Activation of the slow afterhyperpolarization (AHP), which is generated by potassium channels probably located at the proximal region of both apical and basal dendrites, reduced the amplitude measured at the soma of the proximal intrinsic pathway PSPs more effectively than PSPs that were generated distally by the afferent fibers. Thus the amount of reduction by AHP was used as a measure for the relative distance of PSP-generating sites from the soma. In neurons from trained rats, despite the previously reported reduction in AHP amplitude, AHP conductance shunted the PSPs from both synaptic pathways more efficiently compared with neurons from the control rats. We suggest that in neurons from trained rats PSPs are electrotonicly closer to the soma.