Biomedical subjects

Inbar Brosh

Publications and source records attributed to Inbar Brosh.

4 recordsLinked to original sources

PubMed2006

Learning-induced reversal of the effect of noradrenalin on the postburst AHP.

Pyramidal neurons in the piriform cortex from olfactory-discrimination-trained rats have reduced postburst afterhyperpolarization (AHP), for 3 days after learning, and are thus more excitable during this period. Such AHP reduction is caused by decreased conductance of one or more of the calcium-dependent potassium currents, I(AHP) and sI(AHP), that mediate the medium and slow AHPs. In this study, we examined which potassium current is reduced by learning and how the effect of noradrenalin (NE) on neuronal excitability is modified by such reduction. The small conductance (SK) channels inhibitor, apamin, that selectively blocks I(A)(HP), reduced the AHP in neurons from trained, naïve, and pseudotrained rats to a similar extent, thus maintaining the difference in AHP amplitude between neurons from trained rats and controls. In addition, the protein expression level of the SK1, SK2, and SK3 channels was also similar in all groups. NE, which was shown to enhance I(AHP) while suppressing (S)I(AHP), reduced the AHP in neurons from controls but enhanced the AHP in neurons from trained rats. Our data show that learning-induced enhancement of neuronal excitability is not the result of reduction in the I(AHP) current. Thus it is probably mediated by reduction in conductance of the other calcium-dependent potassium current, sI(AHP). Consequently, the effect of NE on neuronal excitability is reversed. We propose that the change in the effect of NE after learning may act to counterbalance learning-induced hyperexcitability and preserve the piriform cortex ability to subserve olfactory learning.

Animals↗

PubMed2004

A molecular mechanism for stabilization of learning-induced synaptic modifications.

Olfaction is a principal sensory modality in rodents, and rats quickly learn to discriminate between odors and to associate odor with reward. Here we show that such olfactory discrimination (OD) learning consists of two phases with distinct cellular mechanisms: an initial NMDAR-sensitive phase in which the animals acquire a successful behavioral strategy (rule learning), followed by an NMDAR-insensitive phase in which the animals learn to distinguish between individual odors (pair learning). Rule learning regulates the composition of synaptic NMDARs in the piriform cortex, resulting in receptors with a higher complement of the NR2a subunit protein relative to NR2b. Rule learning also reduces long-term potentiation (LTP) induced by high-frequency stimulation of the intracortical axons in slices of piriform cortex. As NR2a-containing NMDARs mediate shorter excitatory postsynaptic currents than those containing NR2b, we suggest that learning-induced regulation of NMDAR composition constrains subsequent synaptic plasticity, thereby maintaining the memory encoded by experience.

Animals↗

PubMed2004

Learning-induced long-term synaptic modifications in the olfactory cortex.

The idea that memory is manifested at the cellular level by enhancement of synaptic connections between simultaneously activated neurons has been suggested half a century ago by Hebb, and is widely accepted since. Much effort is done to describe such enhancement and reveal the underlying mechanisms. Learning-induced synaptic modifications were studied in the last decade with in-vitro brain slices preparations. Several forms of long-term enhancement of synaptic connections between layer II pyramidal neurons in the piriform cortex accompany olfactory learning. Such modifications were described also in other brain areas, following other training paradigms. Post-synaptic enhancement of synaptic transmission is indicated by reduced rise time of (post synaptic potentials) PSPs and formation of new synaptic connections is indicated by increased spine density along dendrites of these neurons. Enhanced synaptic release is indicated by reduced paired-pulse facilitation. In slices from trained rats predisposition for long-term potentiation is decreased and predisposition for long-term depression is increased. These modifications are attributed to olfactory-discrimination rule learning, rather than to memories for specific odors, and may be subsequent to intrinsic modifications in pyramidal neurons that create favorable conditions for activity-dependent synaptic enhancement.

Animals↗

PubMed2002

Learning-induced reduction in post-burst after-hyperpolarization (AHP) is mediated by activation of PKC.

We studied the role of protein kinase C (PKC) and protein kinase A (PKA) in mediating learning-related long lasting reduction of the post-burst after-hyperpolarization (AHP) in cortical pyramidal neurons. We have shown previously that pyramidal neurons in the rat piriform (olfactory) cortex from trained (TR) rats have reduced post-burst AHP for 3 days after odour-discrimination learning, and that this reduction is due to decreased conductance of calcium-dependent potassium current. In the present study, we examined whether this long-lasting reduction in AHP is mediated by second messenger systems. The broad-spectrum kinase inhibitor, H7, increased the AHP in neurons from TR rats, but not in neurons from pseudo-trained (pseudo-TR) and naive rats. Consequently, the difference in AHP amplitude between neurons from TR and control animals was diminished. This effect was also obtained by application of the specific PKC inhibitor, GF-109203x. The PKC activator, 1-Oleoyl-2-acetyl-sn-glycerol (OAG), significantly reduced the AHP in neurons from naive and pseudo-TR rats, but not in neurons from TR rats, so that the difference between the groups was abolished. The PKA-specific inhibitor, H-89, increased the AHP in neurons from all groups to a similar extent, and the difference in AHP amplitude between neurons from TR rats and neurons from controls was maintained. We suggest that while the post-burst AHP in piriform cortex pyramidal neurons is modulated by both PKC and PKA, a PKC-dependent process maintains the learning-related reduction of the AHP in these cells.

Action Potentials↗